Devices and methods for tissue immobilization and non-invasive lower urinary tract analysis

ABSTRACT

Provided are devices and methods suitable for immobilizing tissue and for use in non-invasive methods of assessing lower urinary tract symptoms as well as in surgical application.

RELATED APPLICATION

The present application claims priority to U.S. Patent Application61/781,624, “Devices And Methods For Tissue Immobilization And ForNon-Invasive Urinary Tract Analysis,” filed Mar. 14, 2013, the entiretyof which is incorporated herein by reference for any and all purposes.

GOVERNMENT RIGHTS

The subject matter disclosed herein was made with government supportunder an Internal Revenue Service Qualifying Therapeutic DiscoveryProgram (“QTDP”) grant entitled “Non-invasive Urethro-cystometer.” TheGovernment may have certain rights in the herein disclosed subjectmatter.

TECHNICAL FIELD

The present disclosure relates to the field of uroflowimetry, to thefield of urodynamics, and to the field of medical devices.

BACKGROUND

Lower Urinary Tract Symptoms (LUTS) such as urinary frequency, urgency,nocturia, and diminished or interrupted urine flow (sometimes termed“weak stream”) are suggestive of urethral obstruction caused by BenignProstatic Hyperplasia (BPH). Other lower urinary tract disorders (e.g.,bladder dysfunction), however, may present with the same symptoms.Unfortunately, the non-invasive diagnostic tests recommended by theAmerican Urological Association (AUA), including the patient self-reportscale (e.g., the AUA symptom index) and simple office uroflowmeters thatmeasure flow rate during urination are unable to accurately determinethe source of LUTS, especially whether the symptoms are caused byblockage of the urethra due to BPH, or from bladder weakness or someother lower urinary tract condition. A depiction of the lower urinarytract is provided in FIG. 58 attached hereto.

The causes of LUTS are not self-evident. Either a weak bladder (e.g.,neurologic damage) or urethral obstruction (e.g., BPH) can cause “weakstream.” Statistically, in men obstruction is twice as likely as poorbladder pressure, so if a trial on medication is not effective,diagnostic/therapeutic prostate surgery is performed. Surgery helps 2out of 3 patients. However, about 1 in 3 is not helped, and overallabout 1 in 20 has some significant side effect from the procedure. Manydollars are spent each year on unneeded prostate procedures and also onthe cost of managing adverse effects of the unnecessary surgery.

Some procedures, such as urodynamic studies, can diagnose bladderdysfunction, but are not recommended by the AUA because they areinvasive (they involve placement of catheters in the urethra andbladder), and therefore are associated with a significant rate oftrauma, infection and other complications. Further, these invasiveurodynamic procedures require complex equipment and skilled personnel,and are expensive and uncomfortable for the patient, and cannot beconveniently repeated to confirm abnormal findings or to evaluateresponse to treatment.

By age 65 many men have enlarged prostates and eventually about onethird undergo prostate surgery, mostly for management of symptomsthought to be caused by urethral blockage secondary to BPH, otherwiseknown as bladder outlet obstruction (BOO). But after surgery many mencontinue to experience the same LUTS plus additional problems (such aserectile dysfunction and loss of sphincter control secondary to surgicalinjury). Although more than $3 billion is spent each year in the U.S.for prostate surgery (mostly for BPH), one in three surgical proceduresfor BPH does not result in relief of LUTS because the urinary tractsymptoms initially attributed to BPH were caused by factors other thanurethral obstruction.

The expense and risk of existing invasive urodynamic methods make itimpractical to perform pre- and post-operative studies to identifybladder dysfunction and objectively measure response to treatment.Although uroflowmetry is presently considered a suitable noninvasivetest for detecting lower urinary tract dysfunction, the test does notdetermine the cause of the dysfunction or specify a “cutoff” flow valuethat can be used to determine what therapy is appropriate.

In one prospective blind study of uroflowmetry on patients undergoingprostate surgery for LUTS, those patients with peak flow rates above 15ml/s had significantly less symptom relief from prostate surgery,suggesting that in patients with flow rates above 15 ml/s it is unlikelythat obstruction due to BPH is the source of the LUTS. The findingsindicate that for many patients urinary tract symptoms are not due tourethral obstruction, but instead involve dysfunction of the bladder.Other studies have shown that uroflowmetry results were not helpful indiagnosing obstruction due to BPH. Thus, the focus on uroflowmetryplaces an emphasis on a single non-invasive test of questionablediagnostic specificity. Also, nearly all commercially availableurodynamic tests that measure bladder function are invasive, and currentinvasive urodynamic studies also have a poor risk to benefit quotientdue to cost and potential complications. Existing non-invasivetechniques to measure isovolumetric (i.e., maximum or asymptotic)bladder pressure during urination—such as an inflatable cuff attached tothe penis—are inaccurate, painful and also difficult to use in aconsistent manner. Accordingly, there is a long-felt need for anaccurate, simple, safe, painless, low-cost, and non-invasive technologyto determine the source of lower urinary tract symptoms.

SUMMARY

In meeting these long-felt needs, the present disclosure provides, interalia, components. These components suitably comprise a vacuum chamberhaving an entry opening configured to engage with a subject's anatomyproximate to a subject's urethra, the vacuum chamber having an outletport configured to engage with a vacuum source; a urethral engagementconduit extending into the vacuum chamber, the urethral engagementconduit having a proximal opening configured to engage a subject'sanatomy proximate to the subject's urethra, the entry opening of thevacuum chamber and the proximal opening of the urethral engagementconduit defining a gap therebetween, the gap being configured so as toenable passage of the subject's anatomy proximate to the urethra throughthe gap and into the vacuum chamber upon application of sufficientvacuum, the component being configured to give rise to a leak-proofmechanical seal under vacuum between the proximal opening and theanatomy proximate to a urethra upon application of sufficient vacuum;and the component further comprising a receptacle in fluid communicationwith the urethral engagement conduit (e.g., the distal opening of theurethral engagement conduit), the receptacle further comprising areceptacle aperture in some embodiments. Because the disclosedtechnology is non-invasive, it avoids the need for uncomfortable devicesthat are used in existing urological studies, including anal probes,penile cuffs, and the like.

Also provided are systems, the systems suitably comprising a receptacle,a component configured to effect mechanical, leak-proof fluidcommunication between a subject's urethra and the receptacle so as togive rise to a flow circuit; the component comprising a vacuum chamberhaving an entry opening adapted to engage with a subject's anatomyproximate to the subject's urethra. The system may be configured to,under application of sufficient vacuum to the vacuum chamber, effectfluid communication between the subject's urethra and the receptacle,and the system may include a sensor configured to measure a pressurewithin the receptacle.

Also provided are methods, comprising applying sufficient vacuum to avacuum chamber so as to effect passage of a subject's anatomy into thevacuum chamber through a gap between an opening in the vacuum chamberand an opening of a urethral engagement conduit, the vacuum beingapplied so as to effect leak-tight fluid communication between thesubject's urethra and a receptacle; and measuring, as a function of timeduring urine excretion, a pressure within the receptacle.

Additional provided are components, comprising a vacuum chamber, thevacuum chamber comprising a tap or other port adapted for application ofvacuum, and the vacuum chamber defining at least one opening formedtherein, the at least one opening being adapted to, upon application ofsufficient vacuum, securably engage with tissue.

Also provided are methods, the methods comprising contacting a vacuumchamber comprising at least one tissue engagement aperture to a bodytissue; and providing sufficient vacuum to the vacuum chamber so as todraw at least some of the body tissue into the vacuum chamber and so asto physically stabilize at least part of the tissue.

Further provided are components, comprising a vacuum chamber, the vacuumchamber comprising a tap adapted for application of vacuum, and thevacuum chamber defining at least one opening formed therein, the atleast one opening being adapted to, upon application of sufficientvacuum, securably engage with tissue.

Also provided are methods, comprising contacting a vacuum chambercomprising at least one tissue engagement aperture to a body tissue; andapplying sufficient vacuum to the vacuum chamber so as to draw at leastsome of the body tissue into the vacuum chamber and so as to physicallystabilize at least part of the tissue.

BRIEF DESCRIPTION OF THE DRAWINGS

The summary, as well as the following detailed description, is furtherunderstood when read in conjunction with the appended drawings. For thepurpose of illustrating the invention, there are shown in the drawingsexemplary embodiments of the invention; however, the invention is notlimited to the specific methods, compositions, and devices disclosed. Inaddition, the drawings are not necessarily drawn to scale or proportion.In the drawings:

FIG. 1 provides a pressure vs. time plot for Test Patient 1;

FIG. 2 provides a pressure vs. time plot for Test Patient 2;

FIG. 3 provides a pressure vs. time plot for Test Patient 3;

FIG. 4 provides a pressure vs. time plot for Test Patient 4;

FIG. 5 provides a pressure vs. time plot for an exemplary patient;

FIG. 6 depicts a urethral engagement device (UED) according to thepresent disclosure engaged with a glans penis (detail shown in upperregion of figure);

FIG. 7 depicts an exemplary urine receptacle (closed air chamber);

FIG. 8 depicts an exemplary UED (including receptacle and engagementregion) according to the present disclosure (vacuum chamber designed tomechanically trap periurethral tissue and achieve water-tight seal);

FIG. 9 depicts an exemplary pressure measurement system according to thepresent disclosure—a spring and/or hydrostatic pressure may be used toprovide required back-pressure;

FIG. 10 depicts a mechanically-based pressure measurement systemaccording to the present disclosure—a spring and/or air compressionprovide back-pressure;

FIG. 11 depicts data from an exemplary pressure vs. time experiment;

FIG. 12 depicts an alternative system for gathering pressure vs. timeinformation, which may be relevant to methods to measure magnitude oferror due to diabatic processes;

FIG. 13 depicts an exemplary pressure vs. time curve illustratingdiabatic effects;

FIG. 14 depicts a capacitance-based model of the lower urinary tract(LUT), which is one method to measure compliance of LUT;

FIG. 15 depicts exemplary pressure vs. time curves—these can be in somecases corrected for diabatic error to use the initial portion ofpressure-time curve to extrapolate isovolumetric bladder pressure and tomeasure instantaneous urine flow rates and resistance to flow;

FIG. 16 depicts an alternative embodiment of the disclosed technologythat vents urine and features a disposable solenoid valve;

FIG. 17 depicts a capacitance-based model of the urethro-cystometer inwhich one may calculate flow-rate from slope of time-pressure curve, andflow resistance is calculated from inverse slope; Slope=Flow Rate and1/Slope=Resistance;

FIG. 18 depicts a capacitance-based model of the urethro-cystometer; onemay use initial portion of pressure-time curve to extrapolateisovolumetric bladder pressure and to measure instantaneous urine flowrates and resistance to flow—by extrapolating isovolumetric bladderpressure from the lower pressure segment of the pressure-time curve onemay avoid discomfort associated with high back-pressure;

FIG. 19 depicts an exemplary calculation of urinary flow with correctionfor differences in atmospheric pressure;

FIG. 20 depicts an exemplary, non-limiting model to estimate theasymptotic bladder pressure by curve fitting the low pressure segment ofthe pressure-time curve

FIG. 21 presents an exemplary pressure vs. time curve; generated byhydraulic device (phantom patient) that emulates human LUT dysfunction

FIG. 22 presents a curve-fit used to estimate a maximum bladder pressurefrom an actual pressure vs. time curve; analysis of second pressure-timecurve in FIG. 21

FIG. 23 presents another curve-fit used to estimate a maximum bladderpressure from an actual pressure vs. time curve; analysis of third curvein FIG. 21

FIG. 24 presents pressure vs. time data for an exemplary receptacle thatdoes not include a heat sink; using test device exemplified in FIG. 12;note the presence of diabatic error

FIG. 25 presents pressure vs. time data for an exemplary receptacle thatincludes steel wool as a heat sink; using test device exemplified inFIG. 12; note absence of diabatic error

FIG. 26 illustrates an exemplary component suitable for stabilizingtissue in surgical applications;

FIG. 27 illustrates an exemplary component suitable for stabilizingtissue in surgical applications;

FIG. 28 illustrates a cross-section of a component stabilizing tissue ina surgical application;

FIG. 29 illustrates various configurations for components used insurgical applications;

FIG. 30 illustrates an exemplary system according to the presentdisclosure;

FIG. 31 provides an illustration of a component according to the presentdisclosure;

FIG. 32 provides an illustration of a component according to the presentdisclosure;

FIG. 33 provides an illustration of an exemplary closure of a componentaccording to the present disclosure;

FIG. 34 provides an illustration of an exemplary end seal of a componentaccording to the present disclosure;

FIG. 35 provides an front-view illustration of a component according tothe present disclosure;

FIG. 36 provides an illustration of a glans tissue stabilizer accordingto the present disclosure;

FIG. 37 provides an illustration of the various parts of a componentaccording to the present disclosure;

FIG. 38 provides an illustration of a surgical tissue stabilizeraccording to the present disclosure;

FIG. 39 through FIG. 45 provide an illustration of an exemplary flow fora urological assessment according to the present disclosure;

FIG. 46 provides an illustration of an exemplary component according tothe present disclosure;

FIG. 47 provides an illustration of an exemplary component according tothe present disclosure engaged with the glans of a subject;

FIG. 48 illustrates a component according to the present disclosure;

FIG. 49 depicts the portion of an exemplary component that engages withthe subject's anatomy;

FIG. 50 provides an information flowchart for a system according to thepresent disclosure;

FIG. 51 provides a further information flowchart for a system accordingto the present disclosure;

FIG. 52 provides data gathered from an actual patient using thedisclosed technology;

FIG. 53 provides data generated by the phantom patient using thedisclosed technology;

FIG. 54 illustrates a surgical stabilizer according to the presentdisclosure;

FIG. 55 illustrates a system and component according to the presentdisclosure;

FIG. 56 illustrates a component according to the present disclosure,with a close-in view of the vacuum chamber and urethral engagementconduit;

FIG. 57 provides an alternative illustration of the system of FIG. 55;and

FIG. 58 provides a depiction of the lower urinary tract.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

The present disclosure may be understood more readily by reference tothe following detailed description taken in connection with theaccompanying figures and examples, which form a part of this disclosure.It is to be understood that this invention is not limited to thespecific devices, methods, applications, conditions or parametersdescribed and/or shown herein, and that the terminology used herein isfor the purpose of describing particular embodiments by way of exampleonly and is not intended to be limiting of the claimed invention. Also,as used in the specification including the appended claims, the singularforms “a,” “an,” and “the” include the plural, and reference to aparticular numerical value includes at least that particular value,unless the context clearly dictates otherwise. The term “plurality,” asused herein, means more than one. When a range of values is expressed,another embodiment includes from the one particular value and/or to theother particular value. Similarly, when values are expressed asapproximations, by use of the antecedent “approximately” or “about,” itwill be understood that the particular value forms another embodiment.All ranges are inclusive and combinable, and all documents cited hereinare incorporated by reference in their entireties for any and allpurposes.

It is to be appreciated that certain features of the invention whichare, for clarity, described herein in the context of separateembodiments, may also be provided in combination in a single embodiment.Conversely, various features of the invention that are, for brevity,described in the context of a single embodiment, may also be providedseparately or in any subcombination. Further, reference to values statedin ranges include each and every value within that range.

As described elsewhere herein, the present disclosure provides, interalia, a non-steady state approach to analyzing fluid dynamics of complexflow systems. One may then use a computer controlled device forinterrupting flow, and then the instantaneous response of the systemvariables (flow, resistance, compliance, and pressure) is measured asurine flow is repeatedly interrupted.

Components

The measurements are obtained by mating the patient's urethra to aninstrument or system that comprises flow controlling and measuring(e.g., Flow and Pressure Measurement and Control; “FPMC”) components bymeans of a connecting device, which may in some cases be termed aUrethra Engagement Device (“UED”). Analysis of the resultingtime-varying pressures and flows yields values having clinicalsignificance.

The UED (which may be referred to as a component and may, in someembodiments, also be disposable, semi-disposable or reusable) providesan interface between the test subject and other instrumentation. Inmales, the UED attaches to the end of the penis by suction, providing acompletely leak-free seal. If the seal is not leak-proof (e.g., thecomponent has not been properly aligned with respect to the urethra),the user may observe urine collecting in the vacuum chamber (which alsoserves as the urine trap). In such a case, the user may re-align thecomponent relative to the urethra and repeat the testing.

Suction used to form the seal is suitably produced and controlled by avacuum supply subsystem. In some embodiments, a UED may includeconcentric tubes suitably configured to grasp the glans penis. The innertube serves as an extension of the urethra. The size and shape of theinner tube permit the urethral orifice to be fully encompassed and yetbe free to open with minimal resistance to urine flow. The space betweenthe tubes may be evacuated (via vacuum application) to a sub-atmosphericpressure. The glans penis may be coated with a lubricant (e.g., awater-based lubricant) to facilitate passage of glans tissue through thespace between the tubes into the vacuum chamber where the tissue expandsto physically hold the glans in place. Tube ends may be shaped toimmobilize the glans penis, spread open the urethral orifice, andprovide a leak-free seal once the vacuum is applied. As one example, thetube ends may be beveled, curved, angled, or otherwise shaped to moreeasily engage with the subject. The surfaces of the concentric tubesthat engage with a subject are suitably smooth and made of transparentmaterials to facilitate accurate placement of the inner tube around theurethral orifice. A one-size UED fits most males. A suitably designedUED may be used to measure LUT function in females and males withhypospadius. The components are sized and shaped to accommodate anatomicdifferences. Children and animals may also be tested, as the disclosedtechnology is not limited to adult humans.

As one example, a lubricant (e.g., K-Y™ jelly or other lubricant) isapplied to the glans penis and the contacting surfaces of the UED. Avacuum is applied and the glans is centered in the device. The resultingmechanical connection is secure and leak free once a mechanical seal isachieved by drawing peri-urethral tissue through the opening of thevacuum chamber where the tissue may expand and may be physically trappedtherein until the vacuum is relieved, as shown in FIG. 47. Therefore,the urine pressure at the urethral orifice may exceed the vacuum appliedwithout also dislodging the device from the periurethral tissue. In thisway, once the mechanical connection or seal is formed, one may reducethe vacuum. After mechanical connection is achieved, the vacuum need notnecessarily be in excess of the maximum expected bladder pressure (e.g.,about 150 mm Hg), and may suitably be less than the pressure likely torupture capillaries in the glans and result in bruising. FDA approvedvacuum constrictor devices used for treatment of male sexual impotencepermit application to the penis of sub-atmospheric pressures up to 300mm Hg. These pressures may be sustained for up to about 30 minuteswithout adverse consequences in otherwise normal males. The disclosedtechnology may perform a full data collection and analysis in only a fewminutes. The disclosed technology requires only a few minutes tooperate, as it requires only time to attach a UED to a subject and forthe subject to at least partially empty their bladder through the UED.

It should be understood that in some embodiments, only some portion(e.g., the glans penis or even a portion of the glans penis) of asubject's anatomy is inserted within the device. This can improvepatient comfort, as only a small or even minimal amount of tissue isinserted or otherwise engaged by the device.

The UED is a component (which may be disposable, partially disposable,or even reusable) of the disclosed technology. One exemplary UED isshown in FIG. 6. As shown in that figure, a UED may include a vacuumchamber (labeled) and a central urethral engagement conduit (notlabeled). In operation, the UED is contacted to the anatomy proximate toor surrounding a patient's urethra so as to seat the entry of the vacuumchamber around the subject's urethra. A vacuum is applied by way of aport to the vacuum chamber. The vacuum is suitably applied so as to drawperi-urethral tissue into the vacuum chamber through the gap between thevacuum chamber and the urethral engagement conduit, as shown in theupper frame of FIG. 6. The peri-urethral tissue expands, thus creating aleak-proof, mechanical seal between the peri-urethral tissue and thedevice. The port that leads to the urine receiving chamber (closed airchamber) in the air venting UED serves the purposes of, e.g., (a)venting air through a solenoid valve, and (b) measuring pressure withinthe closed air chamber by means of a pressure sensor. Both (a) and (b)are directly connected to the port, and both the solenoid valve and thesensor are part of the FPMC system, the sensor providing the pressuredata used by the FPMC to control the opening and closing of the solenoidvalve, and to generate the pressure-time curves used to calculate theflow rate, the flow resistance, the compliance of the LUT, and theisovolumetric bladder pressure.

As shown in the figure, the proximal end (and opening) of the urethralengagement conduit is suitably disposed at a distance from theperi-urethral engagement opening of the vacuum chamber. The edges ofthese openings may feature lips, curls, and the like. As oneexample—such as that shown in FIG. 6—the edges may feature curls, lips,protrusions, or other features that engage expanded peri-urethral tissueso as to assist in seal formation. As described elsewhere herein, one(or both) of the urethral engagement conduit and the vacuum chamber maybe capable of motion relative to the other. One (or both) of theurethral engagement conduit and the vacuum chamber may also include adeformable material, such as a silicone or other flexible material, suchas a polymer. This may be done so as to facilitate engagement betweenthe device and the subject. Although not shown in the figure, theopening into which the subject's tissue enters may be adjustable, asdescribed elsewhere herein.

Further detail is provided in FIGS. 31-36, which figures provideadditional illustrations of components according to the presentdisclosure. FIG. 31 shows a component according to the presentdisclosure, including the annular space into which the glans may bedrawn and the annular vacuum chamber (or urine trap) on which the vacuumis drawn and into which the user's anatomy may be extended, a vacuumport into the vacuum chamber of the component into which the glans isdrawn, the chamber or receptacle into which urine is excreted, and apressure sensor port in the urine receptacle. FIG. 32 shows thecomponent of FIG. 31, with further illustration of the inclusion of aheat sink material, which can be steel wool or other materials. Glass(e.g., glass wool) and metals are considered especially suitablematerials for this purpose. The end of the component may be sealed witha disposable closure, as shown at the right-hand side of theillustration. One such closure is shown in FIG. 33, which illustratesthat the urine chamber may be closed with a rubber expansion plug-typeseal. Other seals may be used, including polymeric materials, screw-inseals, press-fit seals, interference fit seals, bayonet-type seals,plugs, expander plugs (such as that shown in FIG. 33), and the like;suitable closures will be known to those of ordinary skill in the art.An alternative end seal is shown in FIG. 34, which figure illustrates apress-fit seal; the seal may be cemented into place to create adisposable UED.

FIG. 35 illustrates the subject-engagement end of a component accordingto the present disclosure. As shown in that figure, an annular space isformed between the urethral engagement conduit into which the userexcretes urine and the proximal portion of the component, which may be adonut-shaped region against which the user's anatomy rests during use. Avacuum is applied to the vacuum chamber so as to draw the patient'sanatomy (e.g., the glans) into and in some embodiments through theannular space so as to form a leak-proof seal. The vacuum may be appliedsuch that the patient's anatomy is extended into the volume on which thevacuum is applied. FIG. 36 is an end-on view of a glans tissuestabilizer according to the present disclosure, again showing theannular space into which the user's anatomy is drawn and also the heatsink within the urine excretion chamber. FIG. 37 illustrates the variousparts of a component, including the component, a heat sink material(metal wool), and an end closure used to seal the chamber into whichurine is excreted.

FIG. 46 and FIG. 47 illustrate an exemplary component in operation. FIG.46 illustrates an alternative view of a disposable component accordingto the present disclosure, similar to the reusable component shown inFIG. 32. FIG. 47 shows that same disposable component engaged with asubject. As shown in FIG. 47, a portion of the subject's anatomy hasbeen engaged by the device and is drawn (via vacuum application) throughthe annular space and into the vacuum chamber, thus forming a leak-proofseal between the subject and the device. The subject's urethra (notshown) is now sealably disposed within the urethral engagement conduit,thus placing the subject's urethra (and bladder) into fluidcommunication with the urine receptacle. As shown in other figures,there may be a heat sink disposed within the urine receptacle

FIG. 8 illustrates an alternative component that includes both a UEDsection as well as a receptacle (labeled “closed air space”) into whichthe subject excretes urine. As shown in the figure, the componentincludes a vacuum chamber (which may also be termed a “urine trap”) anda urethral engagement conduit (not labeled), which conduit leads intothe closed air space or urine receptacle. The vacuum chamber suitablyincludes a vacuum tap, which permits application of vacuum to thechamber. The closed air space also suitably features a pressure tap orother outlet that allows the user to monitor the pressure within thechamber. The pressure tap may also be used to vent air from thereceptacle. Not shown—in FIG. 8—is an optional additional tap of theurine receptacle that in turn engages with a valve or other device thatpermits release or venting of urine or air from the urine receptacle, asdescribed elsewhere herein. In some embodiments, the valve (which may bea solenoid valve or a disposable portion of a solenoid valve) isincorporated into the component. In other embodiments, the receptacleincludes a tap or other opening that allows the receptacle to engagewith a valve that is controlled by a device. The receptacle may alsoinclude a port that allows urine to be dumped or otherwise removed fromthe receptacle.

An alternative component is shown in FIG. 7. That component 20 includesa urine receptacle 24 that features a tap 25 that allows for measurementof the pressure within the receptacle 24. The component also includes avalve (bottom of image) that may be configured to release air, urine, orboth from the receptacle. As shown in the figure, urine enters from topof chamber. The side-arm leads to a pressure sensor (e.g., a transducer)that triggers a valve at bottom of chamber to release the pressure (bydumping the urine) when a predetermined pressure level is reached (e.g.,80 mm Hg). The valve then closes and another pressure-flow cycle occurs.These cycles are repeated until the bladder empties and urine flowceases.

FIG. 9 presents another embodiment of the disclosed technology. On theright-hand side of the figure is a urethral engagement or extenderdevice. Such devices are described elsewhere herein. The pictured devicealso includes a piston (center of figure) that is configured to measurethe pressure within the urine receptacle. As shown, a spring may be usedto measure the pressure within the urine receptacle. The device may beconfigured so as to measure the isovolumetric pressure of the bladderwhile the receptacle remains closed to the exterior environment duringurine entry. The non-air-based pressure measuring system avoidstemperature, atmospheric pressure and diabatic issues associated withair-based pressure measuring systems. Thus, FIG. 9 depicts an exemplarypressure measurement system with a fluid-based method to generatetime-pressure curves to measure urine flow rate, flow resistance andisovolumetric bladder pressure during micturition.

Components will now be described in additional detail. In someembodiments, a component may comprise a vacuum chamber having an entryopening configured to engage with a subject's anatomy proximate to thesubject's urethra, the vacuum chamber having an outlet port configuredto engage with a vacuum source. The component may also include aurethral engagement conduit extending into the vacuum chamber, theurethral engagement conduit having a proximal opening configured toengage a subject's anatomy proximate to the subject's urethra, the entryopening of the vacuum chamber and the proximal opening of the urethralengagement conduit defining a gap therebetween, the gap being configuredso as to enable passage of the subject's anatomy proximate to theurethra through the gap and into the vacuum chamber upon application ofsufficient vacuum, the component being configured to give rise to aleak-proof mechanical seal under vacuum between the proximal opening andthe anatomy proximate to a urethra upon application of sufficientvacuum. The component may also include a receptacle in fluidcommunication with the urethral engagement conduit, the receptaclefurther comprising a aperture (also termed “tap” in some cases). Thisaperture may be used to permit monitoring of the temperature, pressure,or both within the receptacle.

The aforementioned gap may comprise a distance (e.g., a radial distance)between an edge of the proximal opening of the urethral engagementconduit and an edge of the entry opening of the vacuum chamber, as shownin, e.g., FIG. 6. This distance is suitably less than about 50 cm, lessthan about 10 cm, less than about 5 cm, less than about 3 cm, or evenless than 1 cm. The gap may also include a vertical distance between aplane of the proximal opening of the urethral engagement conduit and aplane of the entry opening of the vacuum chamber. As one non-limitingexample, the proximal opening of the urethral engagement conduit may liein a first plane, and the entry opening of the vacuum chamber may lie ina second plane. The two planes may be parallel to one another, althoughthis is not a requirement. The vertical distance described above issuitably less than about 50 cm, less than about 5 cm, or less than about3 cm, or even less than about 1 cm, e.g., 0.1, 0.5, or about 0.7 cm.

Another exemplary component is shown in the lower right hand image ofFIG. 16. As shown there, application of a vacuum draws periurethraltissue (in this case, the glans penis) into the gap between the urethralengagement conduit and the vacuum chamber, thus forming a leak-proofseal between the urethra and the urethral engagement conduit. This sealin turn places the urethra into fluid communication with the receptacle.As shown in FIG. 16, the openings of the vacuum chamber and urethralengagement conduit may include lips, curls, and the like that may beadapted to maintain the tissue seal. The vacuum applied to the vacuumchamber is suitably less than 300 mm Hg (e.g., 200 mm Hg, 150 mm Hg, 100mm Hg, 50 mm Hg, 25 mm Hg, and lower), although vacuums above 300 mm Hgmay be used in some instances.

As FIG. 16 further shows (upper frame of figure), the urethralengagement region may be suitably connected to a vacuum sourceconfigured to apply the seal-forming vacuum. The vacuum source may be apump or other device that connects to the component, but the componentitself may also include the vacuum source. As one example, the componentmay include a squeeze bulb, a button, or other device configured toapply a vacuum to the vacuum chamber. The urethra is suitably in fluidcommunication with a receptacle (or “closed air space”), that is sealedto the external environment. A pressure sensor or other sensor issuitably in fluid communication with the interior of the receptacle soas to monitor the pressure within the receptacle. A valve (e.g., asolenoid valve as shown in FIG. 16) is suitably disposed so as torelease urine, air, or both from the receptacle. The valve may bemanually actuated or actuated in an automated fashion by a controller orother device, such as a computer.

In some embodiments, the proximal opening of the urethral engagementconduit and the entry opening of the vacuum chamber are characterized asbeing essentially concentric with one another. Openings may be circularin cross-section, but this is not a requirement, as an opening may beelliptical, polygonal, oblong, or otherwise non-circular incross-section. The openings may overlap with one another, but it is notnecessary that the entirety of one opening overlap with the entirety ofthe other opening, as the openings may be configured so that they areoffset from one another. As one example, a component may be configuredsuch that the entirety of the proximal opening of the urethralengagement conduit does not overlap with the entry opening of the vacuumchamber.

In some embodiments, the entry opening of the vacuum chamber defines afirst cross-sectional dimension and the proximal opening of the urethralengagement conduit defines a second cross-sectional dimension. Across-sectional dimension may be a diameter, a radius, a chord, a span,and the like. The first cross-sectional dimension may be in the range ofbetween about 100% and about 500% of the second cross-sectionaldimension. In some embodiments, the second cross-sectional dimension isgreater than the first cross-sectional dimension by from 0.01% to about500%. In some embodiments, the first and second cross-sectionaldimensions are equal to one another.

The components are suitably constructed of rigid materials, such aspolycarbonate, polystyrene, and other polymers. Although not required,at least one of the vacuum chamber or the urethral engagement conduit issuitably transparent or at least partially transparent. The transparencyfacilitates alignment of the component with the subject and also aids invisualizing the presence—or absence—of urine in the vacuum chamber,receptacle, or both.

The urethra may be aligned with the component in a variety of ways. Oneway to effect alignment is to apply an inked end of a tube havingsuitable proper dimensions to the tip of the penis to create a circularmark to center the component on the glans penis. A transparent componentcan facilitate this alignment. Alternatively, a component may feature aguide (integrated or removable), such as a funnel or other projectionthat places the urethra into proper register with the component. Asdescribed elsewhere herein, the disclosed technology is not limited touse on males, and may be used on females as well as animals.

The component may be formed as a single piece, but the component mayalso comprise an assembly of two or more pieces. It should also beunderstood that although a component may comprise a single material(e.g., a component made entirely from polycarbonate), a component maycomprise two or more materials. As one example, the urethral engagementconduit might be formed from polyethylene, and the vacuum chamber mightbe formed from polycarbonate.

In some embodiments, at least one of the vacuum chamber and the urethralengagement conduit comprises a deformable material, such as a silicone,a polyurethane, and the like. A deformable material may assist in thecomponent engaging with the subject.

The proximal opening of the urethral engagement conduit and the entryopening of the vacuum chamber may be fixed in position. Alternatively,at least one of the proximal opening of the urethral engagement conduitand the entry opening of the vacuum chamber is capable of motionrelative to the other. The relative motion may be effected by advancing(e.g., sliding or screw-advancing) the proximal opening of the urethralengagement conduit relative to the entry opening of the vacuum chamber,by withdrawing the proximal opening of the urethral engagement conduitrelative to the entry opening of the vacuum chamber, or both. At leastone of the urethral engagement conduit and the vacuum chamber may belockably mounted, i.e., may be mounted so that it can be moved and thenfixed into position. In this way, the user may vary the size of theopening to the vacuum chamber through which the user's anatomy passes.

This is depicted in FIG. 49, which figure depicts an exemplary componentaccording to the present disclosure. The left-hand image of the figureshows an end-on view of the component, with a distance d between theinner ring (i.e., the urethral engagement conduit, shown with dottedfill) and the outer ring, which is the portion of the component that isproximate to the user and against which the user's anatomy may rest(shown with solid fill). As shown in the image, there is a space betweenthese two elements, and this space is the space into which a subject'sanatomy is drawn into the vacuum chamber. The space may be annular asshown in FIG. 49, but annular spaces are not required, as the space maybe oblong, slit-shaped, or some other configuration. It should also beunderstood that there may be one, two or more spaces defined betweenthese elements. The separation d shown in FIG. 49 is the distancebetween the two elements, and may be in the range of from about 0.01 mmto about 1 cm, to about 5 cm, about 10 cm, or even about 50 cm, in someembodiments. Values of d between about 0.1 cm and about 2 cm areconsidered especially suitable, but are not essential.

FIG. 49 also shows—right-hand panel—a vertical separation h between theurethral engagement conduit (the lower of the two elements in thefigure) and the proximate portion of the component. As describedelsewhere herein, the distance h may be varied by relative motion of theurethral engagement conduit and the proximal portion of the component;this motion may be accomplished, for example, by advancing the urethralengagement conduit toward or away from the proximal portion of thecomponent. The distance h may be in the range of from about 0.01 mm toabout 1 cm, to about 5 cm, about 10 cm, or even about 50 cm, in someembodiments. Values of h between about 0.1 cm and about 2 cm areconsidered especially suitable, but are not essential.

In some exemplary embodiments, (e.g., FIG. 35 and FIG. 48), the openinginto the vacuum chamber is donut-shaped in cross-section. As shown inthe figure, the size of the opening may be changed by relative motionbetween the portion of the vacuum chamber against which the subject'sanatomy rests and the proximal opening of the conduit.

The entry opening of the vacuum chamber suitably has a cross-sectionaldimension (e.g., diameter) in the range of from about 0.1 cm to about 10cm, about 50 cm, or from about 0.5 to about 5 cm, or even from about 1cm to about 2 cm. The proximal opening of the urethral engagementconduit may have a cross-sectional dimension in the range of from about0.1 cm to about 3 cm, or from about 0.5 cm to about 1 cm.

In certain embodiments, the entry opening of the vacuum chamber, theproximal opening of the urethral engagement conduit, or both, defines anadjustable cross-sectional dimension. A cross-sectional dimension may beadjusted by an iris-type opening, by an opening formed in a deformablematerial, and the like. A component may have a proximal portion (with anaperture) that is removable and that can be replaced with a proximalportion that has an aperture of different sizes.

The receptacle suitably has an interior volume in the range of fromabout 0.1 ml to about 100,000 ml, or from about 1 ml to about 1000 ml,or even from about 20 ml to about 500 ml.

The components may be designed so as to have a weight of less than about10 kg, less than about 5 kg, less than 1 kg, or even less than 0.5 kg.

The component may be cylindrical in form, but this is not a requirement.The component may have an external cross-sectional dimension (length,width, diameter, radius) in the range of from about 1 cm to about 100cm, or from about 10 cm to about 25 cm. Components sized to be handledby a single technician are considered especially suitable. The componentmay include a handle, ridges, or other surface feature configured toassist in handling the component.

A component may also include a heat-absorbing material, which materialmay be disposed in, on, or around the receptacle. Suitableheat-absorbing materials include metals (e.g., copper, brass, steel),glasses, and the like. Materials in “wool” or fibrous form—such assteel, copper or glass wool—are considered especially suitable for thedisclosed components. The heat-absorbing material may be solid, but mayalso be a foam or otherwise include pores, voids, and the like. Liquidheat-absorbing materials are also considered suitable. Fibrousmaterials—such as glass wool—are especially suitable for use in thedisclosed components. The heat absorbing material may also be disposedsuch that the material is in thermal communication with the interior ofthe receptacle. As one non-limiting example, the heat-absorbing materialmay be disposed on the outside of the receptacle. One or more conductingstructures—e.g., a rivet—may be used to place the interior of thereceptacle into thermal communication with the exterior of thereceptacle or even with a heat-absorbing material that is exterior tothe receptacle.

Components may, in some embodiments, include a valve that is configuredto place the interior of the receptacle into fluid communication with anenvironment exterior to the interior of the receptacle. The valve may bedisposed at the receptacle aperture. It should be understood that thereceptacle aperture may be used to place the interior of the receptacleinto fluid communication with a valve exterior to the receptacle or to apressure sensor exterior to the receptacle. The valve may be a solenoidvalve, a butterfly valve, or other type of valve. The valve may bemanually actuated, but is also suitably actuated be an automated device.One such example is shown in FIG. 9, which shows a solenoid valveintegrated into a component according to the present disclosure. Thesolenoid shown in FIG. 9 is shown for illustrative purposes only, asother kinds of valves (butterfly, ball, and the like) can be used.

Components may, as described elsewhere herein, also include a vacuumdevice in fluid communication with the outlet port of the vacuumchamber. Suitable vacuum devices include hand pumps, squeeze bulbs,motorized devices (e.g., vacuum pumps) and the like. The vacuum deviceis suitably manually-actuated, but may also be automated or evenself-powered.

In some embodiments, the disclosed components include a pressure sensorcapable of fluid communication with the interior of the receptacle, atemperature sensor capable of thermal communication with the interior ofthe receptacle, or both. In some embodiments, the pressure sensor, thetemperature sensor, or both, is comprised in a transmitter device. Asone such example, the transmitter device may be an RFID device or otherdevice capable of transmitting data (e.g., pressure readings) from thecomponent sensor to a receiver or other device. In this way, a componentmay collect temperature, pressure, or other information and then providethat information to a user.

Components according to the present disclosure may also include acompliant structure configured to deform in response to the presence offluid in the receptacle. Such a structure may be a balloon, aspring-actuated structure, a deformable membrane, a column of fluid, orany combination thereof. FIG. 9 presents one such component. As shown inFIG. 9, a spring is in fluid communication with the interior of thereceptacle, and increasing pressure in the receptacle acts to compressthe spring. Compression of the spring may then be correlated to apressure within the receptacle.

FIG. 10 presents another alternative embodiment. As shown in thatfigure, urine may enter (left side of figure) a receptacle. Thereceptacle may be kept closed (i.e., sealed) to the external environment(by keeping the valve at the right side of the figure) closed so as toeffect urination into an closed system. As urine enters the component,the atmosphere inside the closed component exerts against theaccordion-type reservoir, which in turn exerts against a spring. Thespring (in a vented chamber) in turn compresses against a sensor, whichin turn reports a value that represents the instantaneous pressurewithin the receptacle. Although the valve in this figure is configuredto release urine from the receptacle, it should be understood that avalve may be positioned or otherwise configured (e.g., by placing thevalve at the top or headspace of the receptacle) so as to release airfrom the receptacle. The disclosed components may use either an air ornon-air based pressure measuring system. The use of an air-based systemmay benefit from compensation or control over temperature, atmosphericpressure and diabatic effects, although this is not a requirement.

Exemplary pressure vs. time curves are shown at the bottom of FIG. 10.As shown, each curve shows an increase in pressure within the componentwhile the component is closed to the exterior environment, followed by adecrease in pressure to zero (i.e., atmospheric pressure) when urine,air, or both are released from the system by way of the valve beingactuated. The valve then closes during urination to re-seal thereceptacle against the exterior environment, and the pressure within thereceptacle again rises. The cycle may then be repeated during urination.

As described elsewhere herein, the air, urine, or both may be releasedwhen the pressure within the receptacle reaches a maximum value. Themaximum value will represent the maximum pressure achieved by thesubject's urine flow, which also represents the maximum pressure thesubject's bladder achieves. This maximum pressure may be determined bymonitoring the pressure within the receptacle. Alternatively, the air,urine, or both may be released when the pressure within the receptaclereaches a predetermined value (e.g., 30 mm Hg) that may be less than themaximum. Although this is not a requirement, this approach has theadvantage of reducing or eliminating potential discomfort experienced bythe subject from painful stretching of the distal urethra which is notaccustomed to exposure to high isovolumetric bladder pressures.Curve-fitting techniques and other methods of calculation (describedelsewhere herein) can be used to calculate or estimate a maximum bladderpressure from a pressure vs. time curve (e.g., a curve gathered frompermitting the subject to urinate into the receptacle and then releasingurine or air from the receptacle when the receptacle reaches somepredetermined internal pressure e.g., 40 mm Hg) that does not includethe maximum pressure. Also as shown in FIG. 10, a user may include acorrection for diabatic effects in the pressure vs. time curves.

A component may also include a flow resistance device capable of fluidcommunication with the urethral engagement conduit. The component willhave its own inherent flow resistance (e.g., by virtue of the aircontained in the component), but may also include a further flowresistance device. Such a device may be a capillary, a membrane, orother flow resistor. The flow resistance device may have a variable flowresistance. As one such example, the flow resistance device may includea valve, obstruction, constriction, or other aspect that may bemanipulated to as to vary the flow resistance of the device. In the caseof the air filled receptacle (i.e., the UED closed air chamber) theresistance to urine flow into the UED is provided by the back-pressurecreated by the compliance of air (or other gas) under compression fromthe urine entering the closed chamber. This behavior is consistent withthe gas laws. In the case of the urine venting UED the air volume withinthe air chamber at atmospheric pressure remains the same from onepressure-time curve to the next, so air compliance (and resistance toflow) remains the same throughout the test. However, with the airventing UED, the urine displaces a given volume of air from the closedair chamber with each pressure-time curve, and compliance of theremaining air at atmospheric pressure decreases (and resistance to flowincreases) from one pressure-time curve to the next.

The present disclosure also contemplates that the component (e.g., thereceptacle) may have a fluid or solid or gas disposed within. The fluidmay be water, alcohol, artificial urine, an antiseptic, or other fluid.The fluid may be used to calibrate the UED, establish a vapor pressure,a humidity, or other condition within the component. The solid may be aheat sink (as described elsewhere) or a space occupying solid to changethe volume of the closed air space or to calibrate the UED. Thecomponent may also include a conductive material that provides heat tothe component. This may be in the form of a metallic band that surmountsat least a portion of the component, which metallic band may be heatedso as to heat the component. A component may accordingly be adapted tobe heated before use, e.g., to be heated to body temperature, as with alaboratory oven or other heating device. A component may even include aresistor (e.g., wire) configured to supply heat to the device. Acomponent may also contain within (e.g., be pre-loaded with) a gas, suchas water vapor, alcohol vapor, or other gases so as to provide a vaporpressure within the component.

Using induction heating with the steel wool heat sink will permit rapid,smooth and easily regulated heating of the closed air space within thedisposable. The greater the mass of the heat sink, and the greater thevoltage/current, the quicker the increase in temperature and the betterthe stability in temperature after the current is turned off

A component may include a vacuum chamber that defines an interior volumein the range of from about 0.01 ml to about 100 ml, about 500 ml, oreven about 1000 ml. It should be understood that a component may, insome embodiments, comprise a vacuum chamber without a urine receptacle.As one such example, a component might include an annular ordoughnut-shaped vacuum chamber that itself has a circular opening. Sucha component may be used to releasably attach to, for example, thesurface of the beating heart to stabilize the operative field duringcoronary artery procedures. Alternatively, such a component may be usedto releasably attach to tissue such as skin, blood vessels, cardiactissue, or other forms of tissue, in a manner akin to stretchingmaterial across the frame of a tambourine. In this way, the componentfixes and immobilizes tissue so as to stabilize that tissue within thepatient and to enhance the ability of surgeons to operate on or aroundthe stabilized tissue.

As shown in FIG. 28, a region of the tissue is stabilized by virtue ofthe tissue being drawn into the vacuum chamber. A component may beattached to a bracket or brace; in this way, when the component attachesto the heart or other tissue, it also acts to attach—and evenimmobilize—the heart or other tissue to the bracket or brace. The vacuummechanically traps tissue, which trapping yields a mechanicallystabilized region of the tissue that can be more easily (and safely)operated upon. Relieving the vacuum in turns allows the tissue to bereleased from the component. As described elsewhere herein, thestabilized region of tissue need not necessarily be round, as it may besquare, triangular, oblong, or some other shape. An additional view isshown in FIG. 54. That figure shows a stabilizer engaged with the skinof a patient, showing the skin being drawn up into the annular vacuumchamber of the stabilizer, with additional skin being held in tensionacross the “hole” of the annular stabilizer device. The vacuum port isshown at the right-hand side of the image, showing a vacuum tubeconnected to the port of the device so as to provide a vacuum to thevacuum chamber of the stabilizer device. It should be understood thatthe annular device shown in FIG. 54 is exemplary only and does not limitthe shape of the device, as devices may be square, oblong, or some othershape.

The component may be sized so that it defines a cross-sectionaldimension (or even a maximum cross-sectional dimension) of from about0.01 cm to about 50 cm, or less than 10 cm, less than 5 cm, or even lessthan 2 cm. For example, the component may have a diameter (defined bythe inner diameter of the inner ring of the device) of about 3 cm and aheight of about 0.5 cm. The component may be configured and sized to asto be insertable into a patient by way of an incision or even aso-called keyhole incision. The component may also comprise a deformablematerial so that at least a portion of the component may be compacted orotherwise folded to ease insertion into a patient and to ease transitwithin the patient to the desired location. The component may include adeformable material and a rigid material, in some embodiments. A devicemay be configured so that it expands or otherwise opens once insertedinto a patient. In some embodiments, a component may be fabricated ofsubcomponents that are connected or otherwise assembled with one anotheronce they are placed within a subject. A component may be constructed soit takes on a curved or other shape within a patient, as needed. Thedevices may be constructed such that their shape, curvature, or othercharacteristic may be adjusted while the device is inside of a patient;i.e., be adapted to the operative field in terms of curvature and shape.The component may also be connected to a flexible or rigid conduit orother connection that provides the vacuum to the component once thecomponent has been inserted into the patient. The component may also beconnected to another component, device, or connection that holds thecomponent in place. Once the component is positioned, the user may applya vacuum (suitably less than about 300 mm Hg, 100 mm Hg, 50 mm Hg, 10 mmHg, or even less than about 5 mm Hg) so as to affix the component to thetissue of interest. The vacuum connection may define a cross-sectionaldimension (e.g., diameter, radius) in the range of from about 0.01 mm toabout 10 mm or even about 50 mm. The component may also be positioned soas to—when vacuum is applied—seal or otherwise clamp off a blood vesselor other structure. It should be again understood that the opening ofthe vacuum chamber may be circular, but may also be of another shape,such as square, oblong, elliptical, or other shape.

Exemplary devices (not necessarily to scale) are shown in FIG. 26 andFIG. 27. As shown in those figures, a component may be annular in shape.A tap (outlet) is formed in the device so as to connect the vacuumchamber to a vacuum source. The devices shown in these figures have anannular gap into which the tissue is drawn. An annular gap is not arequirement, as the gap may be slots (e.g., opposed slots), a square, atriangle, and the like, as shown in FIG. 29. The device may even includeonly a single gap or slot into which tissue is drawn.

The component may include a first opening to the vacuum chamber and asecond opening to a tissue aperture; as described above, the tissue issuspended and fixated across the tissue aperture. The first opening mayhave a cross-sectional dimension in the range of from about 0.1 cm toabout 10 cm or even about 20 cm. The second opening may have across-sectional dimension in the range of from about 0.1 cm to about 10cm or even about 20 cm. The first opening is suitably larger than thesecond opening, although the two openings may be of the same size. Asdescribed elsewhere herein, the component may define a gap between thetwo openings, which gaps are described elsewhere herein.

These disclosed components have application in, e.g., cardiac surgery.The heart-lung machine permits temporary paralysis of the heart muscleand provides a relatively blood-free operative field, therebyfacilitating the surgical repair of coronary vessels, valves andcongenital cardiac defects. However, there are draw backs to theheart-lung machine, mostly related to adverse effects on the CNS.Alternative methods include mechanically immobilizing the beating heart.When heart surgery is performed without using the heart-lung machinethere are fewer intra-operative complications and less post-operativemorbidity. A number of mechanical devices have been developed toimmobilize the portion of the heart undergoing surgery. These large andcomplicated devices require the chest to be opened as in heart-lungprocedures, and they squeeze the heart, resulting in muscle damage andreduced cardiac output.

Computerized methods have been developed to permit keyhole surgery onthe beating heart. The surgeon sits at a console, observing thepatient's heart on his video screen while manipulating the surgicalinstruments by remote control. The computer moves the instruments insync with the heart movements so the surgeon can operate as if the heartwas not beating. The use of key-hole surgery further reducespost-operative complications and recovery time, but the technology iscomplicated and fraught with danger. An improved method for immobilizingthe heart that would also facilitate key-hole surgery is to be desired.

The disclosed components address this problem by enabling mechanicalfixation of the area of the heart to be operated upon, but withoutcompromising cardiac output or traumatizing the heart muscle. The devicecan be used in either open chest or key-hole procedures. This technologymethod will result in fewer CNS complications (e.g., embolism andstroke) than found with the heart-lung machine. It also facilitatesmicrosurgical vascular and valvular repair procedures by physicallyimmobilizing the beating heart without compromising cardiac output ortraumatizing the heart muscle. An additional image is shown in FIG. 38,which figure illustrates an exemplary tissue stabilizer. As shown in thefigure, such a stabilizer may include an inner ring and an outer ringthat define a space therebetween. A vacuum port is then used to apply avacuum to the space therebetween so as to draw the subject's tissue intothat space and to stabilize the tissue circumscribed by that space. Theexemplary component shown here is circular in configuration, but othershapes—e.g., any polygon, oval, and the like—may be used as well. In oneexemplary embodiment, the component may be toroidal in configuration, asshown in FIG. 38. The tissue-engaging edges of the component may becurved, beveled, or squared, depending on the needs of the user. Asexplained elsewhere herein, the component may include one or moreflexible regions so as to facilitate deployment of the component on thesubject. If needed, multiple devices may be applied to an organ, such asa beating heart, to stabilize the organ as well as the local tissue.

In addition, a component may include an extension configured to reduceblood flow when the component is engaged with a subject. Such anextension may be a clip, a bar, a spring, or other similar structurethat may reduce blood flow (e.g., by at least partially closing off ablood vessel) in the region nearby to the device. As one non-limitingexample, the component may include a clip that closes off a blood vesselthat is upstream or otherwise nearby to the component when the componentis deployed in the patient. The extension may thus be used to reduce oreliminate blood flow at or around the tissue being stabilized.

Systems

The present disclosure provides systems. The systems may include, e.g.,an apparatus (e.g., an instrument) for flow and pressure measurement andcontrol, which may be termed the Flow and Pressure Measurement andControl (FPMC) system. An FPMC may include systems for controlling andmeasuring instantaneous urine flow rate (uroflowmetry) and bladderisovolumetric pressure (urodynamics). The apparatus is controlled by,and the output recorded by, a subsystem consisting of a computer withappropriate system control and data acquisition hardware and software.At the conclusion of each test, the computer performs a data analysisand parameter calculation program, which solves flow model equations toprovide readout of contribution of urethral obstruction (e.g., bladderoutlet obstruction due to BPH)) and bladder weakness to the observedurinary tract dysfunction. As described elsewhere herein, FIG. 58provides a depiction of the lower urinary tract and of the bladder- andobstruction-related causes of LUTS.

FIGS. 39-45 depict exemplary operation of an FPMC system. FIG. 39provides an exemplary flow of information. In that figure, a user may(1) choose a patient from the database or creates a new patient file forthe database. The user can run a new trial or analyze a patient'spreviously recorded trial; (2) begin collection of pressure data fromthe device. Collections ends at the user's discretion, and the trial maybe saved to the patient's file; and (3) process the raw pressure data asa series of pressure curves. The user can determine a portion of the rawdata to be processed. FIG. 40 depicts an exemplary information-flow forpressure, showing how a user may record, comment, and save the data.

FIG. 41 depicts an exemplary pressure analysis process. In thatexemplary figure, a user may (1) perform data selection; (2) curveextraction; (3) fitting and extrapolation, and (4) flow analysis. FIG.42 depicts an exemplary system configuration panel interface, in which auser may set parameters for the acquisition and analysis processes. Asdepicted in FIG. 43, a user may set a number of acquisition parameters,including sampling rate, maximum pressure, solenoid valve open time,terminal configuration, timeout, tolerance, and minimum pressureparameters.

FIG. 44 depicts a variety of analysis parameters; some exemplaryparameters include DAQ filter parameters, effective zero pressure, curveerror tolerance, number of data points, atmospheric pressure, andinitial air volume. It should be understood that this listing ofparameters is illustrative only and is not restrictive or limiting. Auser may use some, all, or even none of these parameters.

FIG. 45 shows a variety of exemplary curves obtained from an exemplarysystem according to the present disclosure. As shown, a user may cropraw data to be processed. After processing each pressure curve andaveraging the results, the following is plotted: Extrapolated Curve,Flow Rate (dp/dt), Flow Resistance (dt/dp), Flow Rate vs. Pressure, andFlow Resistance vs. Pressure. By applying Boyle's Law to the pressuredata, both Volume (ml) and Flow Rate (ml/s) are calculated and plottedto verify the extrapolated results.

FIG. 50 provides an exemplary information flow for an exemplary system.As shown, a variety of variables (shown on the “Configuration Variables”panel of the figure) may be considered in the system. As shown, apressure sensor or pressure array may be adjusted to reflect zeropressure, and a pressure array may be preprocessed with a low-passfilter. The system may engage in an extrapolation process, in which datapoints are analyzed and then fit to an exponential (or other) model,which may be accomplished using a least-squares analysis. The system mayalso perform flow analysis processes, as shown in the figure. Curves andvalues of interest (e.g., asymptotic bladder pressure) may be displayedto the user.

FIG. 51 provides an exemplary DAQ (data acquisition) informationflowchart. As shown in the “Configuration Variables” panel, a number ofvariables may be considered by the process. A user may begin samplingdata, with the system collecting pressure data as a function of time andalso managing the opening of a solenoid (or other) valve as needed tovent the interior of the urine receptacle. The trial data may be savedto a patient's file in a database.

Systems may, as described elsewhere herein, include a receptacle, acomponent configured to effect mechanical, leak-proof fluidcommunication between a subject's urethra and the receptacle so as togive rise to a flow circuit; the component comprising a vacuum chamberhaving an entry opening adapted to engage with a subject's anatomyproximate to the subject's urethra, the system being configured to,under application of sufficient vacuum to the vacuum chamber, effectfluid communication between the subject's urethra and the receptacle;and a sensor configured to measure a pressure within the receptacle.

Suitable components are described elsewhere herein; components accordingto the present disclosure are suitable for use in the disclosed systems.A component suitably includes a urethral engagement conduit having aproximal opening.

Systems are suitably configured to effect, under application ofsufficient vacuum, passage of the anatomy proximate to the urethra intothe vacuum chamber through a gap between the entry opening of the vacuumchamber and the proximal opening of urethral engagement conduit. Thecomponent suitably comprises the receptacle, although this is not arequirement, as the receptacle may reside in a device with which thecomponent engages.

The system suitably includes a vacuum source, which vacuum source may bein fluid communication with the vacuum chamber. Suitable vacuum sourcesinclude pumps, squeeze bulbs, and the like.

A system also suitably includes a release device that is adapted torelease urine, air, or both from the receptacle. The release device maybe, e.g., a solenoid valve, a butterfly valve, a ball valve, and thelike. The release device may engage with the component. For example,this may be by way of an aperture, tap, or other connection to thereceptacle. As described elsewhere herein, the release device may becomprised in the component. A system also suitable includes a deviceconfigured to controllably actuate the release device. As one example,the system may include a servo, a magnet, solenoid coil, or other aspectthat acts to actuate the release device. The system is suitablyconfigured to controllably actuate the release device.

In some embodiments, the system includes a component (which may bedisposable) that engages with a subject and then also engages with ananalysis/control device. The component, as described elsewhere herein,may include a urethral engagement region, a urine receptacle, or both.In other embodiments, however, at least one of the urethral engagementregion and receptacle are part of an analysis/control device. In theseembodiments, the user may clean out (e.g., sterilize) the urethralengagement region and/or receptacle between patients. Alternatively, thesystem may comprise a disposable urethral engagement region, adisposable receptacle, or both.

An exemplary system is shown in FIG. 55. That figure shows a componenthaving a vacuum chamber connected via a tube to a source of vacuum. Thecomponent also includes a receptacle (into which a subject may excreteurine). The receptacle includes a port that places the interior of thereceptacle into fluid communication with the environment exterior to thereceptacle. In this instance, the port is connected to a pressure sensorthat may monitor the pressure within the receptacle. The port is alsoconnected to a valve that may release pressure from the interior of thereceptacle.

FIG. 56 provides a close-in view of the component of the system in FIG.55. The component in FIG. 56 includes a vacuum chamber and a port to thevacuum chamber; the port is connected to a tube that supplies a vacuumto the chamber. The component also includes—as described elsewhereherein—a receptacle. The receptacle includes a port that places theinterior of the receptacle into fluid communication with the environmentexterior to the receptacle. As shown, the port is connected toadditional tubing, which tubing places the port into fluid communicationwith additional elements.

FIG. 57 presents the system of FIG. 55 in an alternative view. As shownin this figure, the port of the vacuum chamber is connected to a vacuumtube that supplies vacuum to the chamber. The receptacle port isconnected to a pressure sensor and a release valve. The sensor providesreceptacle pressure information to the system, and the system may beconfigured to control the release valve.

Systems may also include a device configured to measure or estimate avolume of urine excreted by a subject into the receptacle. Such a devicemay be a scale (that weighs urine excreted into the component).Alternatively, the system may be configured to measure the slope of apressure vs. time curve, from which the system may calculate the flowrate of urine excreted into the receptacle.

The disclosed systems also suitably include a device configured tomeasure a pressure within the receptacle. Such a device may be apressure sensor, a spring, a balloon, a column of fluid, and the like,any of which may be used to measure a pressure within the receptacle.

Systems may be configured to, for example, calculate a maximum pressureof a urine stream excreted into the receptacle, measure a maximumpressure of a urine stream excreted into the receptacle, or both. Tomeasure a maximum (isovolumetric) bladder pressure, the systemdetermines the pressure within the receptacle at the point that urineflow stops, at which point bladder pressure equals the back-pressurewithin the receptacle. Since measuring isovolumetric bladder pressurecan be painful to the subject, it is advantageous to be able tocalculate the maximum (asymptotic) pressure of the bladder from thelower pressure segment of the back-pressure curve To calculate a maximumpressure, a curve-fitting as shown in FIG. 20 may be applied. In oneexample, an asymptotic maximum pressure may be calculated by measuringthe slope of the pressure vs. time curve when the pressure within thereceptacle is 20 mm Hg and again when the pressure within the receptacleis 40 mm Hg, or else by continually measuring the slopes at each pointon the selected portion of the time-pressure curve. By applying theseslopes to arrive at an asymptotic curve fit, the user may then calculatethe asymptotic maximum isovolumetric pressure that the subject's bladdercan produce. Alternately, if the relationship between back-pressurewithin the closed air space and urine flow rate into the closed airspace is linear, as in the current system, then the bladderisovolumetric pressure can be calculated by measuring the initial urineflow rate at zero back-pressure (atmospheric pressure), then measuringthe back-pressure at 50% of the initial flow rate and multiplying thatpressure by 2. Because the relationship between flow rate and pressureis linear, any convenient ratio can be used to extrapolate theisovolumetric bladder pressure. Put another way, because pressure vs.flow curve is linear, there is a simpler method of calculating theisovolumetric bladder pressure directly from the initial low pressureportion of the pressure-flow curve.

Curve fitting—e.g., to calculate the asymptotic isovolumetric bladderpressure—may be accomplished in a number of ways. One way to model thedisclosed systems is to apply an electrical/physical model, i.e.,charging a known capacitor (using urine to compress a known volume ofair in a closed receptacle) with the combination of an unknown seriesresistor (unknown amount of urethral obstruction due to an enlargedprostate) using a battery of unknown voltage (urinary bladder of unknownstrength of contraction). The solution is derived from analysis of thetime-pressure curve of the back-pressure generated as the patienturinates into the closed air space under the assumption that the bladderisovolumetric (asymptotic) pressure (battery voltage) remains constantduring much of micturition. Once the asymptote is calculated, all theother parameters can be calculated relative to the asymptote. The slopeat any point reflects flow rate and the inverse slope representsresistance to flow (obstruction). The relative contribution ofresistance to flow (obstruction due to prostate enlargement) andstrength of contraction (bladder weakness) can be partialled out fromthese calculations. The test is non-invasive, painless and can beperformed in less than one minute. A number of curve-fitting equationscan describe the time-pressure curve; equations that describe thephysical model are considered especially suitable.

One such approach applies the following model: y=[a*exp (−x/tau)]+c. Inthis model (based on the differential equation used to describe the flowof electrons into a charging capacitor), a is the curve amplitude, x istime in seconds, tau is the time constant, and c is the asymptoticpressure. (Tau is the time needed for the curve to achieve ca. 63% ofthe maximum pressure.) In another model (e.g., FIG. 22 and FIG. 23), thefollowing model is used: Y=A*In (X+B), in which Y is pressure, X is timein seconds*100, and A and B are coefficients particular to a givensystem.

Without being bound to any particular theory, because Boyle's law dealswith absolute temperatures and pressures (atmospheric+gauge) the changesin atmospheric pressure may be considered in the disclosed technology.Atmospheric pressure may be measured and mathematically compensated inthe calculations. As to temperature fluctuations, the potential effectcan be mathematically compensated for by, e.g., using a thermistorinserted through the wall of the closed air space, or a RFIDincorporated within the closed air space.

Because the airspace inside a device may be at a constant temperature,then the compression of the air by another fluid is an adiabaticprocess. Therefore, it is governed by the Boyle's Law, P x V=constant,where pressure and volume are inversely related. Bladder pressure as afunction of time, may be expressed in the following model:pressure(time)=amplitude*e ^((−time/tau))+pressure_(asymptotic)

In one aspect, the disclosed technology may apply a multivariate linearregression model to fit low-pressure data to the generalized exponentialmodel. This linear regression model may be expressed as followsy=b₀*x₀+b₁*x₁. Using a General Least Squares (GLS) Fit function(GenLSFit from the National Instruments Advanced Analysis Toolkit)solved with the Singular Value Decomposition (SVD) algorithm, one maydetermine the two coefficients b₀ and b₁, where b₀ is the amplitude andb₁ is the asymptotic bladder pressure. This function may produce a fitwith the smallest Mean Squared Error (MSE). In the linear regressionmodel, x₀ is e^((−time/tau)) and x₁ is a constant 1. Since tau, the timeconstant, is given for the linear regression model, an iterative leastsquares fit determines the value of tau (to a specified precision) byminimizing the MSE. After this process is complete, then the applicationhas successfully best fit a pressure curve to the exponential model.Given raw input of multiple successive pressure curves, one may firstfilter discrete curves from the raw data. Each curve is fitindependently, and then they are all averaged together. Flow rate andflow obstruction are derived from the extrapolated pressure data. Flowrate is determined by the change in pressure vs. time, which is exactlythe derivative of the exponential model. Flow obstruction is determinedby taking the inverse of the flow rate.

Again without being bound to any particular theory, anotherconsideration in a pressure vs. time curve of micturition (urination)into a closed air space is due to LUT (lower urinary tract) compliance.LUT compliance may be measured by temporarily increasing a known volumeof the closed air space (e.g., initially 100 ml of air) by another knownvolume (e.g., adding another 100 ml of air) during micturition. Theresult is several time-pressure curves at 100 ml and several at 200 mlof air. Deviation from the expected time-constant ratio (e.g., 2:1)reveals an amount of unknown LUT compliance. Solving the resultingcapacitance charging equations (described elsewhere herein) may be usedto derive a LUT compliance correction factor. Although not necessary, anaccuracy (e.g., pressure) of +/−10% is useful for a parametric clinicalmeasure. For example 100 mm Hg (range 90-110 mm Hg=normal bladder)versus 50 mm Hg (range 45-55 mm Hg=weak bladder) is clinicallyinformative. For practical purposes there is no difference between 90and 110 mm Hg isovolumetric bladder pressure. The measure of LUTcompliance may also have clinical significance. The air venting UED candirectly generate a measure of LUT compliance because it seriallydecreases the compliance of the closed air space with each iteration ofthe pressure-time curve as urine collects in the space and displaces airfrom the receptacle.

As to the amount of the time-pressure curve to use to extrapolateasymptotic pressure (isovolumetric bladder pressure) and flow resistance(bladder outlet obstruction), volunteers can often tolerate 80-100 mmHg. There is no discomfort until back-pressure exceeds 60 mm Hg. Avariety of methods, e.g., Lab Fit™, can perform non-linear regressionfor curve fitting the time-pressure curves. Even with all the sources oferror-variance (atm. pressure, temperature, LUT compliance, etc.) anumber of 2 parameter exponential equations were highly predictive(r2>0.999). For example, a suitable fit was made by Y=A*Ln(X+B). A usermay filter or edit out the high frequency artifacts (caused by “waterhammer” when valve or solenoid opens and closes) especially at the verybeginning of each time-pressure curve. Other curve-fitting models arealso suitable, as Y=A*Ln(X+B) is not the exclusive way in which toperform curve fitting.

As described elsewhere herein, an electrical model is useful, i.e., thetime-voltage curve (time-pressure) or time-current (time-flow) curve ofcharging a capacitor of known capacitance (representing a closed airspace of given volume) through an unknown resistor (representing BladderOutlet Obstruction due to enlarged prostate) from an unknown DC voltagesource (representing isovolumetric bladder pressure) with an unknowncapacitor (representing LUT compliance) in parallel. The asymptoticvoltage can be extrapolated and the resistance calculated by solving thespecific exponential equation that describes the time-voltage curve.Without being bound on any particular theory, the expected behavior ofthe hydraulic system emulates the above electrical model, and curvefitting supports this hypothesis.

An exemplary model of a system according to the present disclosure isshown in FIG. 14. That figure presents a system analogized to anelectrical capacitance model, which analogy may be used to calculateasymptotic values and other quantities.

More specifically, the pressure in a urine receptacle (i.e., pressureeffected by excretion of urine into the receptacle) may be analogized tothe voltage applied to a capacitance circuit. The voltage (pressure) isconnected to some resistance, which may be considered an obstruction orother resistance to urine flow. A known capacitor (or capacitors) mayalso be connected to the voltage/pressure. Unknowns in the systeminclude the maximum voltage (bladder pressure) as well as an unknowncapacitance (compliance/resistance of the LUT). By gathering pressurevs. time data at known compliances, the user can measure acompliance/resistance of the system by calculating the slope of thepressure vs. time curve, and can also estimate the asymptotic maximumpressure exerted by the bladder.

This is further shown in FIGS. 17 and 18, which figures presents thevoltage-pressure analogy, within which presents the bladder pressure(voltage) and urethral resistance (resistance) as unknowns that arecalculated by curve-fitting pressure vs. time data.

A system may also be configured to calculate a volume of urine excretedinto the receptacle, to measure a volume of urine excreted into thereceptacle, or both. Calculation may be effected by calculating a slopeof a pressure vs. time curve, which slope in turn yields a flow rate,which can then be used to calculate a volume of urine. Measurement ofthe volume may be effected by visually measuring the amount of urineexcreted into the receptacle, by weighing the urine excreted into thereceptacle (e.g., by weighing the receptacle before and after urination)and converting that weight difference into a volume. The slope of thepressure vs. time curve at any point on the curve serves as a measure ofthe instantaneous flow rate under the specific conditions of bladderpressure and urethral resistance to flow. The inverse slope of thepressure vs. time curve serves as an instantaneous measure of urethralresistance under various pressure and flow conditions, and theasymptotic bladder pressure (at zero flow) provides a measure of bladderfunction (strength, weakness). The system may be used to calculate ormeasure volumetric flow in other living and non-living hydraulic andmechanical systems (as for example, hydraulic models of the humanLUT—“Phantom Patients”).

Systems may also calculate a compliance of the lower urinary tract, tomeasure a compliance of the lower urinary tract, or both. Compliance maybe expressed, e.g., in terms of a slope of a pressure vs. time curvethat presents pressure within the receptacle as a function of time. Asystem may also be configured to calculate a maximum pressure of a urinestream excreted into the receptacle based on a measurement of one ormore pressures within the receptacle, as described elsewhere herein. Thesystem may be used to calculate or measure compliance in other living ornon-living hydraulic or mechanical systems.

A system may also include, e.g., a device configured to recordreceptacle pressure as a function of time, a device configured todisplay receptacle pressure as a function of time, or both. Such devicesmay be memory components (e.g., flash memory), LED screens, liquidcrystal screens, and the like.

The flow circuit of the system may—as described elsewhere—include a flowresistance device. The flow resistance device may have a variable flowresistance. Receptacles may include a heat-absorbing material, asdescribed elsewhere herein.

A system may also be configured to measure urine pressure within thereceptacle, urine stream flow rate, or both, at intervals greater orless than about 1 second, or even less than about 0.5 seconds, less than0.2 seconds, and even less than about 0.1 seconds.

Systems may be configured to release urine, air, or both from thereceptacle in response to a pressure within the receptacle of less thanabout 200 mm Hg, or even less than about 50 mm Hg. This may be done, forexample, to prevent the subject from experiencing discomfort from apressure at their distal urethra. In such a case, the system may releaseair, urine, or both at a receptacle pressure of, e.g., 80 mm Hg or less.As explained elsewhere herein, the system—or a user—can calculate amaximum asymptotic receptacle pressure from data obtained at receptaclepressures of less than that maximum asymptotic pressure. As explainedelsewhere herein, however, the system may measure an actual maximumpressure, i.e., the maximum asymptotic pressure obtained when thesubject excretes (isovolumetrically) into the component and receptacle.The system may also be used to release other liquids or gases fromliving and non-living hydraulic and mechanical systems.

Systems may also be configured to apply a correction for diabaticeffects, temperature effects, atmospheric effects, or any combinationthereof on the receptacle. As shown in FIGS. 11, 12, 13, and 15, thepressure within a receptacle may experience a temporary spike inpressure followed by a diabatic decay. This may be accounted for by thesystem. The system may also be used to correct diabatic effects,temperature effects, atmospheric effects or any combination thereof inother living and non-living hydraulic and mechanical systems involvingcompressing and decompressing gasses.

In some embodiments, a device may self-calibrate. As one example, astandard urological method (such as a uroflowmeter) may be incorporatedinto a system NUD to automatically correct measurement errors (such asdiabatic processes) introduced by the air-based pressure measuringsystem. A built-in uroflowmeter (capacitance, load cell, rotational,etc.) can be added to a system.

There are various methods of analyzing and correcting the back-pressuredata for diabatic and other sources of error, although it is notnecessary to account for or even compensate for them, First, theinstantaneous slope at any point in time on the uroflowmeter volumetricflow curve (representing the actual instantaneous flow rate) provides apoint-by-point correction for the instantaneous slope of theback-pressure curve (which represents the erroneous instantaneous flowrate) at that same point in time, if both are simultaneously recorded atX (e.g., 100) data points per second. The point-by-point correctionprovides the actual urine flow rate (corrected slope) at that givenback-pressure (under the specified conditions of urine flow rate,resistance to flow and bladder isovolumetric pressure). This correctedinstantaneous flow rate data also permits calculation of the correctedinstantaneous resistance to flow (corrected inverse slope) and thepressure asymptote (isovolumetric bladder pressure) to be accuratelycalculated.

One may also extract the foregoing information directly from theuroflowmeter volumetric flow curve by plotting the instantaneous uroflowdata point-by-point against the simultaneous back-pressure data. Theresulting curve is the corrected flow vs. pressure data. Curve fittingthe corrected flow-pressure data generates the corrected instantaneousresistance to flow and the pressure asymptote.

In some embodiments, a test involves only the low pressure segment(e.g., 0 to 60 mm Hg) of the complete (e.g., 0 to 120 mm Hg)back-pressure curve, so flow is maximum at the beginning and decreasesas back-pressure builds up till the vent opens at the selected lowpressure (e.g., 60 mm Hg) to dump air (or urine) from the closed airchamber, and the back-pressure curve (e.g., 0 to 60 mm Hg) is repeatedover and over till the test ends. An independent measure ofinstantaneous urine flow rate recorded concurrent with the back-pressurecurve permits each slope point on the back-pressure curve to becorrected for the actual instantaneous urine flow, also correcting theinstantaneous flow resistance (amount of obstruction) and the curveasymptote (isovolumetric bladder pressure).

Alternatively, the actual total volume of urine collected during thestudy would be measured. This volume of urine reflects the total areasubsumed by all the time-pressure curves generated during the study,minus the subsumed area attributable to diabatic pressure and othererrors. The actual flow rate is calculated at the beginning and end ofeach time-pressure curve (of the multiple time-pressure curves during astudy) and each time-pressure curve is curve-fitted to create adescriptive equation. In the case of urine-venting, the time-pressurecurves would be essentially the same, as the volume of the closed airchamber would remain the same between each time-pressure curve. In thiscase the time-pressure curve equations are averages to increaseprecision of extrapolation of the complete time-pressure curve from theinitial low pressure segment. In the case of air venting there would becompliance changes in the closed air chamber between each time-pressurecurve (as accumulating urine displaces the air), so each curve wouldhave a distinct equation in which one parameter would be a measure ofurethral compliance.

Also, as described elsewhere herein, a heat-absorbing material (alsotermed “heat sink”) may be used to reduce or even eliminate thesediabatic effects. The heat sink may be used to increase the heatcapacity of the component (or receptacle) by at least about 0.1%, 1.0%,5%, 10%, 50%, 100%, 200%, 500%, 1000%, 5000%, 10000%, or by even more.In this way, the heat sink absorbs heat energy generated by compressionof air within the closed air space that might otherwise raise thetemperature within the receptacle resulting in pressure measurementerror. The heat sink may serve to moderate or even eliminate diabaticand/or other temperature effects due to compression and de-compressionof a gas.

The effect of a heat sink is shown by exemplary FIG. 24 and FIG. 25.FIG. 24 illustrates that for an exemplary receptacle that does notinclude a heat sink, diabatic effects contributed to sizeable (20%+)transient changes in pressure at compression and release. FIG. 25illustrates that when a heat sink (steel wool, bronze wool or glasswool) was present in the receptacle, these effects were greatly reducedor eliminated.

As shown in FIG. 11, pressure vs. time curves may be influenced bydiabatic effects (from the compression and de-compression of thecontents of the receptacle during operation), temperature effects,atmospheric pressure effects, and the temperature of the urine excretedinto the chamber; data from air-based pressure measuring system mayinclude errors that can be controlled, compensated and corrected. FIG.19 presents an exemplary calculation showing, using Boyle's law, acalculation of the volume of urine that must be excreted into a chamberof 100 ml volume and also a chamber of 200 ml volume to raise thepressure within the chamber 100 mm Hg above atmospheric pressure, forexample, from 760 mm Hg to 860 mm Hg absolute pressure. Barometricpressure is measured and these effects accounted for and incorporatedinto analysis of the pressure vs. time curves. A barometer may be usedto correct pressure-time curves for variations in atmospheric pressure

FIG. 12 presents an exemplary embodiment of a system according to thepresent disclosure. A syringe, pump, or other device may be connected toa 3-way valve that connects the syringe to a water reservoir (tosimulate urine) and a receptacle. A pressure sensor is configured tomeasure the pressure within the receptacle, and a valve (e.g., asolenoid) is configured to release the contents of the receptacle. Asshown in the exemplary pressure vs. time curves at the bottom of FIG.12, diabatic effects can result in a temporary change in temperature(and hence) pressure upon urine entry into a closed receptacle as wellas another temporary change in pressure upon urine (or air) release.These effects can be accounted for by incorporating them into acurve-fitting algorithm or by adding or subtracting some amount from acollected pressure value in a pressure vs. time curve.

FIG. 13 provides further depiction of exemplary diabatic effects on apressure vs. time curve. As shown in the left-hand side of the figure,diabatic effects lead to a rapid reduction of temperature (and hencepressure) following introduction of fluid in a receptacle. Followingrelease of air, fluid, or both from the receptacle (right-hand side offigure), diabatic effects again lead to a temporary change intemperature (and hence pressure). It should be understood thataccounting for and/or correcting for diabatic effects is a capability ofthe disclosed technology, but is not required for operation of thedisclosed technology.

FIG. 15 provides further presentation of diabatic effects on a pressurevs. time curve. As shown in the upper frame, urine enters a closedreceptacle, causing an increase in pressure within the receptacle.Diabatic effects result in a temporary change in temperature (and hencepressure), which then resolves as temperature and pressure reach anequilibrium. A valve (here, a solenoid) then opens, releasing air,urine, or both. The pressure then falls (suitably to atmosphericpressure), the solenoid closes (suitably during continued urination),and the system then begins collecting the next pressure vs. time curve,as shown in the right-hand side of the upper frame of FIG. 15. Any ofthe pressure vs. time curves may be used as the basis for the disclosedmethods, although a user may wish to use data from the second cycle andsubsequent cycles, as those cycles may contain data that has beencollected at conditions that are more equilibrated than the first cycle.

As further shown in FIG. 15, the shape of the pressure vs. time curvesmay, in some cases, combine diabatic and gas law effects. But theasymptotic pressure estimated from one or more pressure vs. time curvesyields a suitable value for the isovolumetric bladder pressure, and onemay account for, or eliminate sources of error, such as diabaticprocesses, changes in atmospheric pressure, changes in temperature dueto introduction of urine at body temperature. Thus, as shown, diabaticerror may change the shape of the curve (creating error in flow andresistance measures) but can give the correct isovolumetric pressure ifback pressure is permitted to increase to asymptote, althoughisovolumetric bladder pressure can be uncomfortable in some cases forthe distal urethra. One may eliminate diabatic error so as to permitextrapolating isovolumetric pressure from initial portion ofpressure-time curve.

An exemplary system is shown in FIG. 30. That figure shows a component(that includes a receptacle) mounted or otherwise engaged with a devicethat coordinates or otherwise controls monitoring and/or urine or airrelease from the component. The system may include a display (e.g., aCRT, LED, or other display) that allows a user to visualize pressure vs.time curves or other data (e.g., asymptotic maximum bladder pressure,flow rate, flow resistance, etc.) and means to record and print out thedata and analysis. The system may include a touchscreen, keyboard,mouse, pointer, or other control devices. A system may bebattery-powered or plug into an electrical system. The system may behard wired and/or use secure non-wired means of communication.

As shown, a system may be portable. The system may be on wheels for easeof movement. A system may also be manually-portable; as one example, thesystem may be sized so that it may be carried in a bag, suitcase, orother carrying case. In this way, the system may be portable so it canbe transferred between examination rooms or even transferred betweenfacilities.

Methods

The present disclosure also provides methods. The methods suitablyinclude applying sufficient vacuum to a vacuum chamber so as to effectpassage of a subject's anatomy into the vacuum chamber through a gapbetween an opening in the vacuum chamber and an opening of a urethralengagement conduit, the vacuum being applied so as to effect leak-tightfluid communication between the subject's urethra and a receptacle; andmeasuring, as a function of time during urine excretion, the pressurewithin the receptacle.

The methods may include calculating or measuring a maximum pressure ofthe urine stream. Measurement may be effected by, e.g., measuring themaximum pressure within the receptacle during urination. Maximum bladderpressure may be calculated, for example by, as described elsewhereherein, curve-fitting a pressure vs. time curve of urination so as tocalculate an asymptotic maximum pressure. If the pressure vs. flow curveis linear, then initial urine flow rate may be measured at atmosphericpressure (“0” gage pressure) and then the pressure measured again at 50%of the initial flow rate. Doubling this pressure will give the bladderisovolumetric pressure.

The methods may include releasing urine from the receptacle duringexcretion, releasing air from the receptacle during excretion, or both.The methods suitably include measuring the pressure within thereceptacle during urine excretion while the receptacle is closed to theenvironment exterior to the receptacle. In this way, the user maymeasure the bladder isovolumetric pressure within the receptacle duringurination.

The methods may include measuring the pressure within the receptacleduring urine excretion, followed by releasing urine, air, or both fromthe receptacle, followed by measuring the pressure within the receptacleduring further urine excretion. Urine, air, or both may be released whenthe pressure within the receptacle reaches a specific value, e.g., 200mm Hg, 150 mm Hg, 100 mm Hg, 50 mm Hg, or less.

The disclosed methods may also include measuring the temperature withinthe receptacle. The methods may also include changing the temperaturewithin the receptacle. This may be done during urination, but may alsobe done before urination so as to place the component, receptacle, orboth at or at about body temperature.

The methods also include calculating a flow resistance of the subject'surethra, measuring a flow resistance of the subject's urethra, or both.The methods also include calculating or measuring a compliance of thesubject's bladder, the subject's urethra, or both. As explainedelsewhere herein, the compliance may be expressed in terms of a slope ofa pressure vs. time curve collected during urination.

The methods may also include measuring the pressure within thereceptacle when a flow resistance device (such as those describedelsewhere herein) is present. Such a device may add additional flowresistance beyond the inherent flow resistance of the component andreceptacle. The flow resistance device may have an adjustableresistance. The methods may, in some embodiments, include correcting fordiabatic effects, temperature effects, pressure effects, atmosphericeffects, or any combination thereof on the receptacle.

A user may further prescribe a bladder treatment to a subject thatexhibits LUTS and a maximum isovolumetric bladder pressure that is belowa certain value (e.g., 60 mm Hg) and a flow resistance (or compliance)that is also below a certain value. A user may also prescribe a prostatetreatment for a patient with LUTS if isovolumetric bladder pressure isnormal (e.g., above 80 mm Hg) and flow resistance is elevated.

Exemplary Operation

Patients undergoing uroflometry/urodynamic evaluation with the disclosedtechnology are suitably instructed to come to the office with a fullbladder. The test requires some amount of urine, e.g., 50 mL, 100 mL,150 mL, 200 mL, or more. A full bladder is preferable, but is notnecessary to operation of the technology.

Once in the exam room, a patient may be tested either standing orseated. Bedridden patients may also be tested. The UED is fitted to theend of the urethra (the penis, in the case of male patients), and thepatient is asked to urinate and continue until his bladder is empty.After the FPMC detects the onset of urine flow, the FPMC cycles a valve(e.g., a solenoid valve) according to a preset program.

Initially the valve is closed, which in turn gives rise to urine flowinginto a closed air space of known volume, increasing the air pressure inthe space until a predetermined maximum pressure is generated orcalculated (100 mm Hg indicates a “strong” bladder), or else anasymptote is reached at some lower pressure (an asymptote of less than60 mm Hg suggests a “weak” bladder). At this point the valve opens anddumps the urine, and the valve is immediately closed to initiate anothercycle. The FPMC repeats cycles of opening and closing the solenoid valvewhile concurrently measuring both the time-pressure buildup and urineflow rate until the patient's bladder is empty. The slope of thetime-pressure curve (at a given back-pressure) is a measure of theinstantaneous urine flow rate at that pressure. The inverse slope of thetime-pressure curve (at a given back-pressure) is a measure of theurethral resistance at that pressure. In this way, the non-invasivesystem generates the information from uroflowmetry combined withurodynamics to provide the information about both bladder strength andurethral resistance (e.g., bladder outlet obstruction) needed todetermine the cause (or causes) of LUTS.

Information collected in the conduct of the test generates clinicallysignificant data including:

(a) Asymptotic static pressure measures which reflect bladder strength(i.e., the pressure asymptote of the pressure-time curve is the bladderisovolumetric pressure at zero flow after subtracting hydrostaticpressure head). At the asymptote, the pressure in the UED equals bladderpressure plus hydrostatic pressure, and bladder pressure comprisesintra-abdominal pressure plus detrusor pressure;

(b) Dynamic pressure-time measures during cycles of pressure buildup andrelief that reflect the interaction between bladder strength andurethral resistance. The inverse slope at any point of the pressure vs.time curve is a measure of resistance through the urethral obstructionat the differential pressure across the obstruction (e.g., BOO, orbladder outlet obstruction due to BPH), which is bladder pressure plusthe hydrostatic pressure minus the back-pressure in the UED. Thepressure drop across the obstruction at any given flow rate is a measureof resistance to flow, and the pressure drop (resistance) becomes zeroat the pressure asymptote (i.e., at zero flow). Once isovolumetricbladder pressure at zero flow is known, one can calculate the actualnumerical resistance of the urethral obstruction from the inverse slopeof the pressure-time curve. There is no need for a nomogram thatprovides only a crude estimate of obstruction vs. non-obstruction (i.e.,non-parametric).

Bladder pressure includes intra-abdominal and detrusor pressure.Intra-abdominal pressure is not an issue with the UED (as with otherinvasive and non-invasive methods) because the driving force across theurethral obstruction is the differential pressure (bladder pressure plushydrostatic pressure minus UED pressure), which is calculated from thepressure-time curve after isovolumetric bladder pressure at zero flow ismeasured.

(c) Other measures that reflect the visco-elastic properties of theurethra and bladder tissues.

One aspect of the disclosed technology is that the technology functionsusing measurement of only a single dependent variable, pressure as afunction of time. No separate uroflowmeter is needed, as flow rate is afunction of the time-pressure curve (dependent on the pre-set volume ofthe closed air space). As a result, there is no phase difference betweenbladder pressure and urine flow measurements. Other existingtechnologies, such as the penile cuff technology, however, areout-of-phase, and use a separate uroflometer to measure urine flow.Because instantaneous urine flow rate and instantaneous bladder pressureare measured simultaneously by the disclosed technology, it is possibleto accurately apply flow models to analyze and interpret the fluiddynamics of the lower urinary tract, and thereby identify and partialout the effects of bladder weakness from the effects of increasedurethral resistance in explaining the reduced urine flow rate in LUTS.

Exemplary Data

The following section describes data collected from both human subjectsand so-called “phantoms” (electronically-controlled hydraulic devicescombining pumps and flow resistors) that are used to model thecharacteristics of the lower urinary tract. These data demonstrate thediagnostic power of the disclosed technology. In each of theseexemplary, non-limiting phantom cases, a solenoid valve was toautomatically open at either a preset high asymptotic pump pressure(e.g., 100 mm Hg) if bladder pressure is “normal,” or at some lowerasymptotic pressure (e.g. 60 mm Hg) if the bladder is “weak.” The pumpoutput could be set to any specified pressure to emulate theisovolumetric pressure of either a strong or a weak bladder. A varietyof linear flow resistors (e.g., capillary tubes) and non-linearresistors (e.g., needle valves) could be inserted in the flow stream toemulate different forms of urethral obstruction. In each case thephantom “urinates” into a closed air space from which the “urine” (orair) is dumped when the solenoid opens.

As shown in FIG. 1, phantom patient 1 exhibits normal bladder pressure(>80 mm Hg) and normal flow rate (>15 ml/s). The high slope value of thetime-pressure curve during each cycle of “urination” indicates lowresistance to flow under conditions of normal bladder pressure, i.e., nourethral obstruction.

The clinical potential of the disclosed technology is apparent whencomparing phantom patient 2 (FIG. 2) and phantom patient 3 (FIG. 3).Note that both phantom patients 2 and 3 present with low flow rate(i.e., comparatively low slope to the pressure-time curve). Phantompatient 2, however, exhibits a normal bladder pressure (i.e., low flowwith normal bladder pressure) as compared to phantom patient 3 (i.e.,low flow with low bladder pressure). Although both phantom patients 2and 3 exhibit the same symptom (i.e., weak stream) with the same lowflow rate, each has a different cause. Phantom patient 2 suffers frombladder outlet or urethral obstruction while phantom patient 3 hasbladder weakness. Distinguishing the source of decreased urine flow isthe main challenge in differential diagnosis of obstruction due to BPH.For phantom patient 3, understanding the reason for the weak stream isthe difference between prescribing a non-invasive medical treatment thatwill address the cause of the patient's weak stream and prescribingunnecessary prostate surgery that may not address the weakened bladderthat is the source of the diminished urine stream. Thus, when comparingFIG. 2 with FIG. 3, one may observe that although both figures showcomparatively low urine flow, these low flows are from different causes;namely that FIG. 2 illustrates low flow due to urethral obstruction, andFIG. 3 illustrates low flow due to bladder weakness.

The diagnostic power of the disclosed technology is further shown byreference to FIG. 4, which figure illustrates data from phantom patient4, which patient presents with very low flow rate, and exhibits both lowbladder pressure and a low slope value, indicative of both bladderweakness and obstruction.

FIG. 5 presents a representative patient record collected using thedisclosed technology. As shown, this patient exhibits a bladder pressure(>80 mm Hg) that is in the normal range after urination initiated. Thereis, however, evidence of urethral obstruction, as the calculated peakflow rates are comparatively low (<15 ml/s). The entire test shown inFIG. 5 required only 60 seconds from initiation of urination to emptybladder. Total urine volume was 250 ml. This is a record of a patientwith LUTS and an analysis of first 5 time-pressure curves shows normalisovolumetric bladder pressure with reduced flow rate from urethralobstruction due to BPH.

FIG. 52 provides a GUI (Graphical User Interface) showing data gatheredby an exemplary air venting system from a patient with LUTS (frequencyof urination and weak stream) successfully treated with tamsulosin (analpha blocker used to treat BOO due to BPH). The test was performed withthe solenoid valve trigger set to vent back-pressure within the closedair space at 50 mm Hg to prevent pain from stretching the patient'sdistal urethra. One may note an increasing width (decreasing flow rate)and decreasing asymptotic pressure of the consecutive pressure-timecurves as the bladder empties. Analysis (curve-fitting) of the secondpressure-time curve gives a normal calculated isovolumetric bladderpressure of 106 mm Hg associated with a normal maximum urine flow rate(>15 ml/s). These numbers suggest that tamsulosin is an effectivemedical treatment for this patient. Patient still has frequency ofurination (note total volume of urine only 120 ml) but his weak streamhas been alleviated. Note that the NUD serves as a convenient objectivemethod to evaluate response to treatment. Also, only a minimal volume ofurine is required to perform this rapid and pain free procedure.

FIG. 53 provides a GUI for a test using a phantom patient with water atroom temp (72 deg. F) in lieu of urine; in this case the test wasperformed with an air venting UED; one may note that the water displacesan equivalent volume of air from the closed air space (urine receptacle)so that air compliance decreases with each pressure-time cycle, and thePFMC program must recalculate the remaining air volume after each airventing in order to use the gas laws to calculate isovolumetric bladderpressure, instantaneous urine flow rate, instantaneous urethralresistance, and instantaneous LUT compliance from the consecutivetime-pressure (i.e., back-pressure) curves. One may compare this recordto FIG. 1 that was generated by venting “urine” so the air volume of theclosed air space remains constant from one pressure-time curve to thenext.

This is an example of normal bladder pressure with low urine flowconsistent with BPH or other source of bladder outlet or urethralobstruction. One may also note that bladder pressure and flow rate buildup rapidly after urination begins, and drop off gradually as the bladderempties. Therefore calculation of peak (isovolumetric) bladderpressures, slopes of the time-pressure curves, and dynamic time-pressureand time-flow parameters are best performed when these measures becomeconsistent (e.g., during the 2nd, 3rd, 4th and 5th pressure cycles inthis sample record). Without being bound to any particular theory, insome cases, the user may elect to use data from points in time afterurination begins, instead of data from the time (i.e., t=0) whenurination begins. As it can take some time for the bladder to developmaximum pressure during urination (the bladder is a smooth muscle andtakes time to achieve full strength), a user may elect to gather data oruse data taken at some time after urine flow starts, not necessarily atinitiation. A user may also elect (see FIG. 5) not to rely on data takenat the end of micturition, as such data may show a lower pressurebecause once the bladder has emptied, the bladder is no longer achievingits full strength. A user may elect to rely on data taken when a bladderhas achieved isovolumetric contraction, which can take some time tooccur. For example, the user may elect to use pressure vs. time datafrom 0.1 seconds, 0.5 seconds, 1.0 seconds, 5.0 seconds, or more afterurination begins. Alternatively, the user may elect to utilize datagathered after the urine receptacle has been vented one or more times tothe environment exterior to the receptacle.

Summary

In summary, the present disclosure provides a number of advancements.First, the disclosed non-invasive urodynamic devices (NUD) providehardware and software. The hardware may include a urethral extenderdevice (UED) that includes (a) the vacuum chamber and (b) a closed airspace. For male patients, the UED uses the vacuum chamber to adhere tothe periurethral tissue of the glans penis and thereby connect thesubject's lower urinary tract (LUT) to the closed air space within theUED into which urine flows during micturition. The electronic hardwaremay also include a flow and pressure measurement and control (FPMC)system as described elsewhere herein. The software for the FPMC systemmay include programs that (a) accept data from input devices (such aspressure-time data from pressure sensors) within or connected to theclosed air space of the UED, (b) process and measure the data, and (c)control output devices (e.g., solenoid valves) that relieveback-pressure created during micturition by venting the closed air spacewhenever a predetermined air pressure (or volume of urine) is detectedin the closed air space. A FPMC may also regulate the vacuum pump andthe solenoid valve used to connect (and disconnect) the glans penis to(and from) the UED.

The disclosed devices also provide improved attachment of the UED tosubject's LUT. Prolonged exposure to high vacuum may result in physicaldiscomfort plus bruising of the glans. The disclosed UED design usesonly an initial vacuum to draw (for male patients) the lubricatedperiurethral tissue of the glans penis through an appropriately sizedand shaped annular space in the proximal part of the UED, and thenceinto the vacuum space where the ring of periurethral glans tissue withinthe vacuum chamber expands to mechanically trap the glans and therebycreate a strong physical attachment and airtight seal. The design of theannular ring also pulls open the urethral orifice and thereby preventsobstruction to urine flow from the meatus. The vacuum may be reduced toa lower level (less than 100 mm Hg in some embodiments) required tomaintain the tissue seal within the vacuum space even with acomparatively high isovolumetric bladder pressure. When the test is overthe vacuum is released and the glans tissue is free to slip out of thevacuum space.

The disclosed methods of attaching devices to tissue may be used tocreate a leak-proof connection between a body orifice and a test device(e.g., UED to glans), or to stabilize tissue during a procedure, modifyblood flow (e.g., compress a vessel) or even to immobilize an operativesite during surgery, as for example, prevent movement of the operativesite during open-chest or key-hole surgery performed on the beatingheart. Current methods for immobilizing the beating heart during surgeryuse clamping devices that can bruise the heart and compromise function(e.g., decrease cardiac output) as well as adversely affect blood flow.

The disclosed technology also addresses devices that may be reusable,disposable, or semi-disposable. The disclosed designs permit the UED tobe disposable (or semi-disposable) because only air (rather than urine)is vented through a solenoid valve with each iteration of thepressure-time curve. An alternate design using disposable solenoid valvecomponents molded into (embedded within) the UED, and non-disposableparts (e.g., solenoid coil) located outside the UED permits urineventing from a disposable UED. Air venting may be preferred in someembodiments due to mechanical simplicity and low cost. As explainedelsewhere herein, more complex mathematical calculations may be usedwith air venting than with urine venting (where the closed air spacevolume remains constant for each consecutive pressure-time curve). Withair venting the urine collects within the closed air space, displacingmore air with each pressure-time curve iteration. The result is serialdecreases in the compliance of the closed air space. An advantage of theair venting method is that analysis of the resulting series ofpressure-time curves permits calculation of the compliance of the lowerurinary tract (LUT) in addition to calculating bladder isovolumetricpressure, urine flow rates and urethral resistance to urine flow. Otherclinically meaningful parameters may also be derived from thepressure-time curves generated from air venting during micturition intothe UED. A special advantage of a disposable UED is that the device andits contents can be disposed of as medical waste without need to cleanand refurbish. Alternately the urine can be drained from the UED intothe toilet before disposal.

A semi-disposable UED may have a removable seal (e.g., expansionstopper) inserted at the distal end of the closed air space that permitsremoval of the enclosed heat sink, etc. and draining of urine from theclosed air space, washing and sterilizing all reusable UED parts, andreassembling the UED. This design permits a variety of specialized heatsinks, space occupying inserts (to modify the volume of the closed airchamber for subjects who produce small volumes of urine duringmicturition), and sensors (e.g., RFID pressure and temperaturetransmitters), etc. to be cleaned and reused. A UED may be designed toaccommodate non-invasive measures of LUT function performed on females,children, infants, and animals. The NUD may be used repeatedly beforeand after treatment to evaluate response to medical and surgicalinterventions for LUT disorders. Also, the use of the NUD is not limitedto the doctor's office or laboratory setting. A simplified version withmeans to record the pressure-time data for later analysis can be placedin the home setting where a properly trained patient may perform thetest on himself. As for example, before and after use of a prescribedtreatment. Because of the ease of use, research to test the efficacy ofnewly proposed pharmacologic or surgical treatments for LUT symptoms mayalso be performed with the NUD.

The distal urethra (DU) does not usually experience significantback-pressure, and obstructing the DU during micturition results inpainful stretching of the DU. Such pain may be demonstrated when a malepinches off urine flow while urinating. Thus, non-invasive devices usedto measure isovolumetric pressure by blocking urine flow areintrinsically painful. One such devices includes the CT3000 cuff device(Mediplus Co.). To eliminate pain caused by exposing the DU to fullbladder pressure, the disclosed NUD design extrapolates theisovolumetric bladder pressure from analysis of the initial low pressuresegment (e.g., <60 mm Hg) of the pressure-time curve. Isovolumetricbladder pressure may be measured or estimated using the NUD withoutexposing the distal urethra to painfully high pressures because thedesign of the UED creates a linear relationship between pressure andflow. Therefore, the low pressure segment of the pressure-time curve canbe used to calculate the isovolumetric bladder pressure by curve fittingthe initial portion of the pressure-time curve or else extrapolatingfrom the initial portion of the pressure-flow curve. If the relation offlow to back-pressure in the closed air chamber is linear, the initialflow rate into the closed air chamber at zero back-pressure (atmosphericpressure) can be used to accurately extrapolate the pressure at zeroflow (isovolumetric bladder pressure). For example, the back-pressuremeasured at 50% of the initial flow is one-half of the isovolumetricbladder pressure.

Compression (or decompression) of air within the urine receptacle mayraise (or lower) the air temperature resulting in diabatic errorincorporated within the pressure-time curve (which provides data forcalculating instantaneous flow rates and flow resistance). However, theisovolumetric bladder pressure measurement was accurate because thediabatic error rapidly resolved once the pressure within the closed airspace equilibrated with the bladder pressure. However, measuring highbladder pressures using the UED were associated with pain fromstretching the distal urethra. This diabatic error problem may beaddress by distributing a heat sink, such as metal wool, within theclosed air space. The heat sink has much greater mass (and de minimusvolume) compared to the air within the closed air space. As a resultthere is little change in air temperature (minimizing diabatic pressuremeasurement error) during compression and decompression of the closedair space. The pressure-time curves are now essentially free of diabaticerror so they can be used to calculate all clinically relevant measuresfrom the initial (pain-free) low back-pressure portion of thepressure-time curve.

What is claimed:
 1. A component, comprising: a vacuum chamber having awall and having an interior volume, the vacuum chamber having a proximalopening defined by a rounded, thickened edge of the wall of the vacuumchamber, the proximal opening being configured to engage with tissueproximate to a subject's urethra, the vacuum chamber having a portconfigured to engage with a vacuum source that is configured to effect avacuum in the interior volume of the vacuum chamber, the vacuum chamberfurther comprising a urethral engagement conduit having a wall and theurethral engagement conduit extending through the interior volume of thevacuum chamber, the urethral engagement conduit having a proximalopening defined by a rounded, thickened edge of the wall of the urethralengagement conduit, the proximal opening being configured to engage thetissue proximate to the subject's urethra such that the urethra isplaced into fluid communication with the urethral engagement conduit,the interior volume of the vacuum chamber being defined between the wallof the vacuum chamber and the wall of the urethral engagement conduit,the rounded, thickened edge of the proximal opening of the vacuumchamber and the rounded, thickened edge of the proximal opening of theurethral engagement conduit extending towards one another and definingan annular gap therebetween, the annular gap placing the interior volumeof the vacuum chamber into fluid communication with the environmentexterior to interior volume of the vacuum chamber, the annular gap beingdimensioned so as to enable passage of the tissue proximate to thesubject's urethra through the annular gap and into the vacuum chamberupon application of a first level of vacuum within the vacuum chamber,and the annular gap being dimensioned so as to maintain, followingapplication of the first level of vacuum, between the annular gap andthe tissue proximate to the subject's urethra a leak-proof mechanicalseal upon application of a second level of vacuum within the vacuumchamber that is lesser than the first level of vacuum, the leak-proofmechanical seal placing the vacuum chamber and the urethral conduit influid isolation from one another.
 2. The component of claim 1, whereinthe proximal opening of the urethral engagement conduit and the proximalopening of the vacuum chamber are characterized as being concentric withone another.
 3. The component of claim 1, wherein at least one of theproximal opening of the urethral engagement conduit and the proximalopening of the vacuum chamber is capable of being advanced or withdrawnrelative to the other.
 4. The component of claim 1, wherein the annulargap has a width of from about 1 mm to about 20 mm.
 5. The component ofclaim 4, wherein the annular gap has a width of from about 3 mm to about7 mm.
 6. The component of claim 1, wherein the annular gap isdimensioned so as to permit passage of lubricated tissue uponapplication of a vacuum of less than 300 mm Hg.
 7. The component ofclaim 1, further comprising a receptacle in fluid communication with theurethral engagement conduit, wherein the receptacle comprises aheat-absorbing material disposed within the receptacle so as to placethe heat-absorbing material into fluid communication with the urethralengagement conduit such that fluid that enters the receptacle contactsthe heat-absorbing material.
 8. The component of claim 7, wherein theheat-absorbing material is characterized as being fibrous, as beingporous, or as comprising voids.
 9. The component of claim 1, furthercomprising a valve configured to place the interior of the receptacleinto fluid communication with an environment exterior to the interior ofthe receptacle.
 10. The component of claim 1, wherein at least one ofthe vacuum chamber or the urethral engagement conduit is characterizedas being at least partially transparent.
 11. The component of claim 1,further comprising a vacuum device in fluid communication with theoutlet port of the vacuum chamber.
 12. The component of claim 1, furthercomprising a pressure sensor capable of fluid communication with theinterior of the receptacle, a temperature sensor capable of thermalcommunication with the interior of the receptacle, or both.
 13. Thecomponent of claim 12, wherein the pressure sensor, the temperaturesensor, or both, is comprised in a transmitter device.